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Knap, P. W., et J. W. Schrama. « Simulation of growth in pigs : approximation of protein turn-over parameters ». Animal Science 63, no 3 (décembre 1996) : 533–47. http://dx.doi.org/10.1017/s1357729800015435.
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AbstractA dynamic model for simulation of growth in pigs was extended by a module to describe protein turn-over in six body protein pools (muscle, connective tissue, liver, blood plasma, gastro-intestinal, and 'other' proteins). The model describes protein deposition in these pools following different growth curves and differential rates of turnover. Growth curve parameters and turn-over rates were obtained from the literature.In growing animals, experimentally measured turn-over rates represent a combination of turn-over of already-present body protein and fractional (repeated) synthesis of newly deposited protein. An attempt was made to distinguish between these processes by varying the values of the fractional rate of synthesis of newly deposited protein (FRSdrp) and of the proportionof maintenance energy requirements not related to protein turn-over (FrcMEmaint), and comparing the simulated outputto the output from the original model without the protein turnover module.The turn-over rate (TRpres)of already present connective tissue protein reached unrealistic values for FRSdep > 2·5 per day, which puts an upper limit on FRSdep.The output from the extended and the original models showed similar patterns for certain combinations of FRSdefl and FrcMEmaint, dependent on the levels of model input variables. For FRSdcp 2·5 perday, these similar patterns have their optimum at FrcME^^ = 0·65, coinciding with FRSdep =2·0 per day. The corresponding TRpres values were 0·060, 0·019, 0·585, 1·492, 0·582, and 0·016 per day for the above mentioned pools.
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Roux, Z. « Incorporating turn-over in whole body protein retention ef.ciency in pigs ». Animal Science 80, no 1 (février 2005) : 71–81. http://dx.doi.org/10.1079/asc40650071.
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The magnitude of the discrepancy between conventional regression estimates of protein retention efficiency and theoretical estimates of synthesis efficiency indicates a major contribution ascribable to protein turn-over in the generally accepted estimates. As protein turn-over is known to be influenced by diet, feeding level and degree of maturity, this suggests the development of an estimator of protein efficiency that can be adapted for such differences. Therefore, based on generally accepted formulas for growth description, a method of estimating protein retention efficiency was developed which is flexible enough to accommodate different diets, feeding levels and degrees of maturity. Moreover, a formula was derived to convert one type of estimate to the other by regarding constant efficiency as equivalent to variable efficiency at the mid point of the estimation interval. Increase in scientific depth to this descriptive approach is provided by a theoretical consideration of a possible mechanism of hormonal control of protein synthesis and breakdown, ultimately expressed as proportionalities to powers of whole body protein (P). Molecular considerations on cellular synthesis and breakdown indicate a difference between breakdown and synthesis powers equal to (2/9)Q. The factor (2/9) is indicated by an argument based on insulinlike growth factor derived activator diffusion attributes by nucleus and body tissue geometries, whileQis equal to the proportion of nuclei activated by insulin-like growth factor. This proportion is likely to be a function of the concentration of growth factor in the blood. Hence, a linear relationship between intake and blood insulin-like growth factor concentration suggests thatQcan be represented by a scaled transformation of intake, 0 ≤Q≤ 1, such that a value ofQ= 1 represents ad libitum intake on a suitable diet andQ= 0 intake at the maintenance requirement. The quantification of breakdown and synthesis power differences by (2/9)Qleads to kP= {1 + [1 − (P/α)(2/9)Q]−1/6}−1, for turn-over related protein retention efficiency (kP), with α the limit value of P at maturity, so that 0 ≤ (P/α) ≤ 1. Experimental estimates, derived from direct estimates of whole body protein synthesis and breakdown at predetermined levels of intake, are in excellent agreement with the theoretical (2/9)Qin the power associated with (P/α) in kP. Furthermore, conventional multiple regression retention efficiencies satisfactorily approximate the turn-over related retention efficiency that can be calculated at a given level of intake for the mid point of the interval covered by the regression estimates.
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Knap, P. W. « Stochastic simulation of growth in pigs : protein turn-over-dependent relations between body composition and maintenance requirements ». Animal Science 63, no 3 (décembre 1996) : 549–61. http://dx.doi.org/10.1017/s1357729800015447.
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AbstractA dynamic model for simulation of growth in pigs, that was extended by a module to describe protein turn-over, was made stochastic in order to simulate groups of pigs with among-animal variation in the maximum daily protein deposition (Pdep, maxK in the minimum lipid to protein deposition rate (Ri/pimin), and in the distributionof body protein over protein pools (muscle, connective tissue, and other proteins). As a result, these simulated pigs show among-animal variation in body protein content and composition. This in turn leads to among-animal variation in energy requirements for protein turn-over and this causes among-animal variation in maintenance metabolizable energy requirements (MEmaint)as a result of variation in body composition.Simulated population means for PieVimax were varied in seven steps from 100 to 250 g/day, with an among-animal variation coefficient of 0·10; the feeding level was also varied in seven steps. Dependent on the levels of these input variables, 100-kg pigs showed within-population standard deviations in body protein and lipid content of 0·31 to 0·54 kg and 1·22 to 2·17 kg, respectively. ME showed a protein-turn-over-related, within-population coefficient of variation of 0·014 to 0·02. Comparisons over populations suggests that a 1·50 proportional increase in Pdep, max (from 100 to 250 g/day) would increase protein-turn-over-related MEmaint by 11 to 15%, from between 470 and 486 to 541 k] ME per kg body weight0'75 per day. The inferences that can be made from this with regard to experimental design are discussed.
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Tesseraud, S., A. Besnard, R. Peresson, J. Michel, E. Le Bihan-Duval et AM Chagneau. « Growth and muscle protein turn-over : effect of genotype and amino acids ». Reproduction Nutrition Development 37, no 3 (1997) : 337–38. http://dx.doi.org/10.1051/rnd:19970320.
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Roux, C. Z. « Incorporating turn-over in whole body protein retention efficiency in cattle and sheep ». Animal Science 80, no 3 (juin 2005) : 345–51. http://dx.doi.org/10.1079/asc41610345.
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AbstractIn pigs the quantification of breakdown and synthesis by powers of body protein led to the estimation of turn-over related protein retention efficiency by the equation kP= {1 + [1 − (P/α)(2/9)Q]−1/6}−1, with α the limit value of whole body protein (P) maturity, so that 0 ≤(P/α)≤1. The factor 2/9 is derived from diffusion attributes indicated by cell and nucleus geometries α and Q represents a scaled transformation of intake, 0 ≤ Q ≤ 1, such that a value of Q = 1 may represent ad libitum intake and Q = 0 the intake at the maintenance requirement. Published observations on finishing steers provide estimates of whole body protein synthesis and breakdown at pre-determined levels of intake in confirmation of the theoretical (2/9)Q power associated with (P/α) inkP. Further confirmation of the (2/9)Q power in cattle follows from satisfactory agreement between an estimate of conventional multiple regression retention efficiency and the turn-over related retention efficiency calculated at the given level of intake, for the mid point of the body mass interval covered by the regression estimate. In addition, a simulation experiment on cattle from the literature gives power estimates of protein breakdown and synthesis in general agreement with those accepted for pigs. Examples on both fine and coarse diets are employed to suggest a general rule for prediction on diets causing submaximal efficiency due to suboptimal intakes.In sheep, evidence derived from estimates of conventional multiple regression efficiencies suggests that the rule (a-b) = (2/9) Q for the calculation ofkPshould be reserved for the description of compensatory growth. Protein retention efficiency for ordinary growth should be described by an adaptation of the rule derived for suboptimal intakes.
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Muramatsu, T., Y. Ueda, T. Hirata, J. Okumura et I. Tasaki. « A note on the effect of ageing on whole-body protein turn-over in goats ». Animal Production 46, no 3 (juin 1988) : 479–81. http://dx.doi.org/10.1017/s0003356100019097.
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In ruminants a dynamic state of protein turn-over has been poorly understood although the methodology of measuring the rate of protein turn-over has recently been advanced to a great extent (Waterlow, Garlick and Millward, 1978). Available evidence suggests that ruminants such as sheep and cows are no exception among various mammalian species when whole-body protein synthesis of adult animals is compared on a metabolic body-weight basis (Waterlow et al., 1978; Reeds and Lobley, 1980).
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Dutra, S., F. Thuillier, D. Darmaun, B. Messing, M. Rongier et J. F. Desjeux. « Protein turn-over assessed by leucine and glutamine fluxes in adult caeliac patients ». Clinical Nutrition 11 (janvier 1992) : 50. http://dx.doi.org/10.1016/0261-5614(92)90213-a.
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Whittemore, C. T., D. M. Green et P. W. Knap. « Technical review of the energy and protein requirements of growing pigs : protein ». Animal Science 73, no 3 (décembre 2001) : 363–73. http://dx.doi.org/10.1017/s1357729800058331.
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AbstractA review of work reported in the literature was used to present quantitative descriptions of protein use in the growing pig. These are detailed in the text, which also points to preferred values, and to anomalies and lacunae. The review was prepared with the objective of allowing from its content the inclusive and quantitative modelling of amino acid requirement. Requirement was approached as the sum of the component factors: maintenance and protein retention. Ileal true digestible protein and amino acid requirements are presented in a form consistent with that forwarded for energy. Thus both energy and protein elements can be conceptualized within a single coherent framework. Priority uses for absorbed amino acids were assumed to be (a) to support endogenous protein losses resultant from the passage of food and incomplete re-absorption prior to the terminal ileum, (b) to replace lost hair and skin, and (c) to cover the basic maintenance losses which will occur as a result of minimal protein turn-over even when protein retention is zero. The bulk of the protein requirement was directly linked to the daily rate of protein retention, for which the linear-plateau response was accepted. For determination of the maximum rate of protein retention the Gompertz function was proposed, although the use of a single value throughout the growth period was not dismissed. The balance of amino acids for protein retention is specified as different from that for maintenance. Central to the approach was the proposal that the inefficiency of use of ileal digested ideal protein, even when not supplied in excess, was an expression of protein losses occurring as a result of protein turn-over. The requirement for the satisfaction of the losses from protein turn-over occurring as a consequence of protein retention, and therefore additional to the requirements for maintenance, was identified. Quantification was attempted with sufficient success to warrant its inclusion into requirement estimation. It was concluded that this element addressed previously inadequately explained protein utilization inefficiencies. Algorithms are presented based upon protein turn-over which appear to be consistent with empirical findings.
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Tyndall, Joel D. A., Bernhard Pfeiffer, Giovanni Abbenante et David P. Fairlie. « Over One Hundred Peptide-Activated G Protein-Coupled Receptors Recognize Ligands with Turn Structure ». Chemical Reviews 105, no 3 (mars 2005) : 793–826. http://dx.doi.org/10.1021/cr040689g.
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Biermann, Esther, Martina Baack, Sandra Kreitz et Rolf Knippers. « Synthesis and turn-over of the replicative Cdc6 protein during the HeLa cell cycle ». European Journal of Biochemistry 269, no 3 (1 février 2002) : 1040–46. http://dx.doi.org/10.1046/j.0014-2956.2001.02746.x.
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Whittemore, C. T., P. W. Knap et D. M. Green. « Technical review of the energy and protein requirements of growing pigs : energy ». Animal Science 73, no 2 (octobre 2001) : 199–215. http://dx.doi.org/10.1017/s1357729800058185.
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AbstractA review of work reported in the literature was used to present quantitative descriptions of energy dispositioning in the growing pig. These are detailed in the text, which points to preferred values, as well as to anomalies and lacunae. The review was prepared with the objective of allowing from its content the inclusive and quantitative modelling of energy requirement. Requirement is approached as the sum of the component factors; maintenance, protein retention and lipid retention. Conventional expressions of maintenance requirement, as some function of pig mass, were found unconvincing in their variety of expression of coefficients and exponents. The review concluded that maintenance is properly related to protein turn-over, and thereby requires at least to include elements of concomitant protein metabolic activity. It was also judged that maintenance costs might be farm-specific. The energy requirements for activity, gaseous losses and disease were identified as important, but unsatisfactory in their quantification. Exploration of the energy costs of uncomfortable ambient temperatures suggested that whilst the responses of the pig are open to sophisticated and relatively exact calculation, the description of comfort remained inexact. The efficiency of retention of lipid by direct incorporation was high and may comprise a substantial proportion of the dietary lipid supply. There was little evidence of variation in the efficiency of utilization of metabolizable energy from carbohydrate for lipid retention. The linear-plateau paradigm for protein retention was adopted. The efficiency of utilization of energy for protein retention measured by a variety of approaches was found to be highly variable, prone to error and the literature confused. It was concluded that the efficiency of use of metabolizable energy for protein retention would be a function of at least: (a) the absorbed substrate being metabolized for the synthesis of body protein, (b) the rate of total protein tissue turn-over associated with the retention of newly accreted protein and not already accounted in the estimate of maintenance, (c) the mass of protein tissue involved in turn-over, and (d) the degree of maturity attained, and any influence maturity may have upon the rate of turn-over of total body protein. Algorithms for energy requirement are presented based upon protein turn-over and these appear to have some consistency with empirical findings.
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Huang, Anming, Leopold Kremser, Fabian Schuler, Doris Wilflingseder, Herbert Lindner, Stephan Geley et Alexandra Lusser. « Phosphorylation of Drosophila CENP-A on serine 20 regulates protein turn-over and centromere-specific loading ». Nucleic Acids Research 47, no 20 (19 septembre 2019) : 10754–70. http://dx.doi.org/10.1093/nar/gkz809.
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Abstract Centromeres are specialized chromosomal regions epigenetically defined by the presence of the histone H3 variant CENP-A. CENP-A is required for kinetochore formation which is essential for chromosome segregation during mitosis. Spatial restriction of CENP-A to the centromere is tightly controlled. Its overexpression results in ectopic incorporation and the formation of potentially deleterious neocentromeres in yeast, flies and in various human cancers. While the contribution of posttranslational modifications of CENP-A to these processes has been studied in yeast and mammals to some extent, very little is known about Drosophila melanogaster. Here, we show that CENP-A is phosphorylated at serine 20 (S20) by casein kinase II and that in mitotic cells, the phosphorylated form is enriched on chromatin. Importantly, our results reveal that S20 phosphorylation regulates the turn-over of prenucleosomal CENP-A by the SCFPpa-proteasome pathway and that phosphorylation promotes removal of CENP-A from ectopic but not from centromeric sites in chromatin. We provide multiple lines of evidence for a crucial role of S20 phosphorylation in controlling restricted incorporation of CENP-A into centromeric chromatin in flies. Modulation of the phosphorylation state of S20 may provide the cells with a means to fine-tune CENP-A levels in order to prevent deleterious loading to extra-centromeric sites.
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Therkildsen, M., B. Riis, A. Karlsson, L. Kristensen, P. Ertbjerg, P. P. Purslow, M. Dall Aaslyng et N. Oksbjerg. « Compensatory growth response in pigs, muscle protein turn-over and meat texture : effects of restriction/realimentation period ». Animal Science 75, no 3 (décembre 2002) : 367–77. http://dx.doi.org/10.1017/s1357729800053145.
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AbstractThe present experiment was designed to evaluate the effect of different time spans of ad libitum feeding of pigs prior to slaughter after a period of restricted feeding on performance and texture characteristics of the meat. Te n litters of five pigs (Duroc ✕ Landrace ✕ Large White crosses) were allocated to five feeding treatments (AA, R28A42, R43A27, R52A18 and R60A10) at the age of 70 days. AA-pigs were given ad libitum a concentrate diet from day 70 to slaughter at day 140 (approx. 100 kg live weight). R28A42, R43A27, R52A18 and R60A10 pigs were given food at a restricted level (0·6 of ad libitum) for 28, 43, 52 and 60 days, respectively, followed by ad libitum feeding for 42, 27, 18 and 10 days, respectively, until slaughter at day 140. All pigs that had been given food at a restricted level for a period (R28A42, R43A27, R52A18 and R60A10) showed a compensatory growth response in the subsequent ad libitum period. However, only pigs on ad libitum for a minimum of 27 days prior to slaughter (R28A42 and R43A27) had carcass weights and muscle mass similar to that of the control pigs (AA) at slaughter. The restricted feeding increased meat proportion, whereas the feeding strategies had no effect on technological meat quality traits (pH24, drip loss and CIE-colour traits: L*, a* and b*). During compensatory growth, protein turn-over was increased and positively related to the length of the ad libitum period as indicated by the concentration of elongation factor-2 (eEF-2) (P < 0·10), the activity of µ-calpain (P < 0·01) and the myofibrillar fragmentation index (MFI) 1 day post mortem in m. longissimus dorsi (P < 0·08) and the solubility of collagen (P < 0·01). Although not significant, the shear force at day 1 followed the same pattern of improvement as the MFI. The concentration of eEF-2 increased at a faster rate following transition to ad libitum feeding than did the activity of µ-calpain. This suggests that muscle protein synthesis increases at a faster rate after change to ad libitum feeding and reaches the same level as in the control pigs (AA) before muscle protein degradation. This time lag between the increase in protein synthesis and degradation could explain the compensatory growth response and it also suggests that in order to use the compensatory growth mechanism to improve tenderness, the optimal time of slaughter may not coincide with the period of highest growth rates, but may occur at a later stage, when muscle protein degradation is maximal. For pigs slaughtered at 100 kg live weight, we expect muscle protein degradation to be maximal some time beyond 42 days of ad libitum feeding prior to slaughter.
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Ruiz-Gómez, Gloria, Joel D. A. Tyndall, Bernhard Pfeiffer, Giovanni Abbenante et David P. Fairlie. « Update 1 of : Over One Hundred Peptide-Activated G Protein-Coupled Receptors Recognize Ligands with Turn Structure ». Chemical Reviews 110, no 4 (14 avril 2010) : PR1—PR41. http://dx.doi.org/10.1021/cr900344w.
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Odolczyk, Norbert, Ewa Marzec, Maria Winiewska-Szajewska, Jarosław Poznański et Piotr Zielenkiewicz. « Native Structure-Based Peptides as Potential Protein–Protein Interaction Inhibitors of SARS-CoV-2 Spike Protein and Human ACE2 Receptor ». Molecules 26, no 8 (9 avril 2021) : 2157. http://dx.doi.org/10.3390/molecules26082157.
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Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) is a positive-strand RNA virus that causes severe respiratory syndrome in humans, which is now referred to as coronavirus disease 2019 (COVID-19). Since December 2019, the new pathogen has rapidly spread globally, with over 65 million cases reported to the beginning of December 2020, including over 1.5 million deaths. Unfortunately, currently, there is no specific and effective treatment for COVID-19. As SARS-CoV-2 relies on its spike proteins (S) to bind to a host cell-surface receptor angiotensin-converting enzyme-2(ACE2), and this interaction is proved to be responsible for entering a virus into host cells, it makes an ideal target for antiviral drug development. In this work, we design three very short peptides based on the ACE2 sequence/structure fragments, which may effectively bind to the receptor-binding domain (RBD) of S protein and may, in turn, disrupt the important virus-host protein–protein interactions, blocking early steps of SARS-CoV-2 infection. Two of our peptides bind to virus protein with affinity in nanomolar range, and as very short peptides have great potential for drug development.
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Knap, P. W. « Stochastic simulation of growth in pigs : relations between body composition and maintenance requirements as mediated through protein turn-over and thermoregulation ». Animal Science 71, no 1 (avril 2000) : 11–30. http://dx.doi.org/10.1017/s1357729800054850.
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AbstractA dynamic model for simulation of growth in pigs, extended to describe thermoregulatory processes, was made stochastic to simulate groups of pigs with between-animal variation in mature body protein (Pα) and lipid mass (Lα), in the potential rate at which mature mass is attained (B⋆), and in the distribution of body protein and lipid over pools and depots. The resulting variation in body composition leads to variation in energy requirements for protein turn-over and thermoregulation, causing between-animal variation in maintenance requirements (MEmaint).Simulated population means for Pα, Lα/Pαand B⋆were varied in three steps each. Excluding unrealistic parameter combinations this led to 33 – 6 = 21 simulated genotypes. Simulated within-population coefficients of variation (CV) were 7, 15 and 3%. Random replicates of each genotype were simulated five times, in climatic conditions that were in turn severely cold, mildly cold (about 5 and 1ºC below lower critical temperature), thermoneutral, mildly hot and severely hot (about 1 and 5ºC above upper critical temperature), during the entire growth period of 23 to 100 kg live weight. Simulated food intake was ad libitum.Simulated thermoneutral within-population standard deviations of body protein and lipid content were 0·21 to 0·46 kg and 0·78 to 2·14 kg at 100 kg body weight. On average, the corresponding values in cold and hot conditions were slightly higher.MEmaintshowed a protein-turn-over-related within-population CV of 1·5% at thermoneutrality. Thermoregulatory action contributed about 4% extra variance in cold and hot conditions but CV values were not affected. A genetic increase in the maximum protein deposition rate from 100 to 250 g/day would increase MEmaintas related to protein turn-over and thermoregulation by 11% at thermoneutrality, and by 6 to 11% in cold or hot conditions. Two relevant groups of genotypes could be distinguished based on the within-population regression coefficients of MEmainton daily or cumulative protein deposition (bdailyPdep, bcumPdep). These ranged from 0·250 to 0·428 kJ/kg0·75 per day per g/day and from 2·77 to 5·45 kJ/kg0·75per day per kg, respectively, in 12 ‘conventional’ genotypes at thermoneutrality. On average, bdailyPdepwas increased by 48%, 20%, –11% and –36% in the other climatic conditions mentioned above, respectively. The corresponding increase of bcumPdepwas 32%, 14%, 8% and 48%. Three fast-growing lean genotypes showed similar bdailyPdepand bcumPdepat thermoneutrality, but much more pronounced increases in cold and hot conditions: 137%, 49%, –12% and + 88% for bdailyPdepand 248%, 108%, 17% and 196% for bcumPdep.It is concluded that differences in body composition traits between pig genotypes do not cause important between-genotype differences in thermoregulatory MEmaint, and that thermoregulatory processes contribute little body-composition-related variation to hot or cold MEmaintwithin most genotypes.The inferences to be made from this with regard to experimental design are discussed. The verification of the above predictions will require a very elaborate and large-scale experiment.
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Zitnik, Marinka, Rok Sosič, Marcus W. Feldman et Jure Leskovec. « Evolution of resilience in protein interactomes across the tree of life ». Proceedings of the National Academy of Sciences 116, no 10 (14 février 2019) : 4426–33. http://dx.doi.org/10.1073/pnas.1818013116.
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Phenotype robustness to environmental fluctuations is a common biological phenomenon. Although most phenotypes involve multiple proteins that interact with each other, the basic principles of how such interactome networks respond to environmental unpredictability and change during evolution are largely unknown. Here we study interactomes of 1,840 species across the tree of life involving a total of 8,762,166 protein–protein interactions. Our study focuses on the resilience of interactomes to network failures and finds that interactomes become more resilient during evolution, meaning that interactomes become more robust to network failures over time. In bacteria, we find that a more resilient interactome is in turn associated with the greater ability of the organism to survive in a more complex, variable, and competitive environment. We find that at the protein family level proteins exhibit a coordinated rewiring of interactions over time and that a resilient interactome arises through gradual change of the network topology. Our findings have implications for understanding molecular network structure in the context of both evolution and environment.
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Ayana Gayathri, R. V., et D. A. Evans. « Culex quinquefasciatus Say larva adapts to temperature shock through changes in protein turn over and amino acid catabolism ». Journal of Thermal Biology 74 (mai 2018) : 149–59. http://dx.doi.org/10.1016/j.jtherbio.2018.03.016.
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Al Tanoury, Ziad, Elisabeth Schaffner-Reckinger, Aliaksandr Halavatyi, Céline Hoffmann, Michèle Moes, Ermin Hadzic, Marie Catillon, Mikalai Yatskou et Evelyne Friederich. « Quantitative Kinetic Study of the Actin-Bundling Protein L-Plastin and of Its Impact on Actin Turn-Over ». PLoS ONE 5, no 2 (15 février 2010) : e9210. http://dx.doi.org/10.1371/journal.pone.0009210.
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Clark, Lilian, John Nicholson et Ronald T. Hay. « Enhancer binding protein (EBP1) makes base and backbone contacts over one complete turn of the DNA double helix ». Journal of Molecular Biology 206, no 4 (avril 1989) : 615–26. http://dx.doi.org/10.1016/0022-2836(89)90570-6.
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Panja, Anindya Sundar, Bidyut Bandopadhyay, Akash Nag et Smarajit Maiti. « Protein Secondary Structure Determination (PSSD) : A New and Simple Approach ». Current Proteomics 16, no 3 (18 février 2019) : 246–53. http://dx.doi.org/10.2174/1570164615666180911113251.
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Background: Our present investigation was conducted to explore the computational algorithm for the protein secondary structure prediction as per the property of evolutionary transient and large number (each 50) of homologous mesophilic-thermophilic proteins. </P><P> Objectives: These mesophilic-thermophilic proteins were used for numerical measurement of helix-sheetcoil and turn tendency for which each amino-acid residue is screened to build up the propensity-table. Methods: In the current study, two different propensity windows have been introduced that allowed predicting the secondary structure of protein more than 80% accuracy. Results: Using this propensity matrix and dynamic algorithm-based programme, a significant and decisive outcome in the determination of protein (both thermophilic and mesophilic) secondary structure was noticed over the previous algorithm based programme. It was demonstrated after comparison with other standard methods including DSSP adopted by PDB with the help of multiple comparisons ANOVA and Dunnett’s t-test. Conclusion: The PSSD is of great importance in the prediction of structural features of any unknown, unresolved proteins. It is also useful in the studies of proteins structure-function relationship.
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Sun, Xiaotong, Hua Jin, Yangyang Li, Haiying Feng, Chunhong Liu et Jing Xu. « The Molecular Properties of Peanut Protein : Impact of Temperature, Relative Humidity and Vacuum Packaging during Storage ». Molecules 23, no 10 (12 octobre 2018) : 2618. http://dx.doi.org/10.3390/molecules23102618.
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This study aimed to investigate the variation of molecular functional properties of peanut protein isolate (PPI) over the storage process and reveal the correlation between the PPI secondary structure and properties in the storage procedure. After storage, the molecular properties of PPI changed significantly (p < 0.05). Extending storage time resulted in a decrease in free sulfhydryl content, fluorescence intensity, surface hydrophobicity and emulsifying properties, which was accompanied by an increase in protein particle size. The results of infrared spectroscopy suggested the content decline of α-helix and β-sheet, and the content rise of β-turn and random coil. Based on bivariate correlation analysis, it was revealed that surface hydrophobicity and emulsifying activity of PPI was significantly affected by α-helix and by β-turn (p < 0.05), respectively. This research supplied more information for the relationship between the peanut protein’s secondary structure and functional properties over the stored process.
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Horne, Jim E., et Sheena E. Radford. « A growing toolbox of techniques for studying β-barrel outer membrane protein folding and biogenesis ». Biochemical Society Transactions 44, no 3 (9 juin 2016) : 802–9. http://dx.doi.org/10.1042/bst20160020.
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Great strides into understanding protein folding have been made since the seminal work of Anfinsen over 40 years ago, but progress in the study of membrane protein folding has lagged behind that of their water soluble counterparts. Researchers in these fields continue to turn to more advanced techniques such as NMR, mass spectrometry, molecular dynamics (MD) and single molecule methods to interrogate how proteins fold. Our understanding of β-barrel outer membrane protein (OMP) folding has benefited from these advances in the last decade. This class of proteins must traverse the periplasm and then insert into an asymmetric lipid membrane in the absence of a chemical energy source. In this review we discuss old, new and emerging techniques used to examine the process of OMP folding and biogenesis in vitro and describe some of the insights and new questions these techniques have revealed.
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Strunk, Bethany S., Noah Steinfeld, Sora Lee, Natsuko Jin, Cecilia Muñoz-Rivera, Garrison Meeks, Asha Thomas et al. « Roles for a lipid phosphatase in the activation of its opposing lipid kinase ». Molecular Biology of the Cell 31, no 17 (1 août 2020) : 1835–45. http://dx.doi.org/10.1091/mbc.e18-09-0556.
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The phosphoinositide phosphatase Fig4 is predicted to turn over the signaling lipid PI3,5P2. It is shown that a major role of Fig4 is to elevate PI3,5P2 via dynamic regulation of the protein complex that activates its opposing lipid kinase, Fab1.
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Shitov, Alexandr V. « An Insight into the Bicarbonate Effect in Photosystem II through the Prism of the JIP Test ». Photochem 2, no 3 (15 septembre 2022) : 779–97. http://dx.doi.org/10.3390/photochem2030050.
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Photosystem II (PSII) is the unique pigment–protein complex that is capable of evolving molecular oxygen using solar energy. The activity of PSII determines the overall productivity of all oxygenic photosynthetic organisms. It is well known that the absence of HCO3− induces a drop in the activity of PSII. However, it is not yet clear what type of photochemical reaction, single turn-over or multiple turn-over, HCO3− is involved in. Kinetic parameters of this (these) involvement(s) are almost unexplored now. This work addresses these issues. Using the JIP test, being the perspective noninvasive method for measuring PSII activity in plants, this paper describes how HCO3− deficiency affects the electron transfer on the oxidizing as well as the reducing sides of PSII in thylakoids and in PSII preparations from the leaves of pea plants. HCO3− was found to be simultaneously involved both in single turn-over and in multiple turn-over events (“dynamical processes”). Moreover, the involvement of HCO3− in dynamical photochemical processes was revealed to be associated with both sides of PSII, being the rate limiting on the reducing side, which follows from obtained kinetic parameters. The involvement of HCO3− in dynamical processes as the constant exchangeable ligand is discussed for both the electron donor and acceptor sides of PSII.
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Fahie, Kamau M. M., Kyriakos N. Papanicolaou et Natasha E. Zachara. « Integration of O-GlcNAc into Stress Response Pathways ». Cells 11, no 21 (5 novembre 2022) : 3509. http://dx.doi.org/10.3390/cells11213509.
Texte intégralRésumé :
The modification of nuclear, mitochondrial, and cytosolic proteins by O-linked βN-acetylglucosamine (O-GlcNAc) has emerged as a dynamic and essential post-translational modification of mammalian proteins. O-GlcNAc is cycled on and off over 5000 proteins in response to diverse stimuli impacting protein function and, in turn, epigenetics and transcription, translation and proteostasis, metabolism, cell structure, and signal transduction. Environmental and physiological injury lead to complex changes in O-GlcNAcylation that impact cell and tissue survival in models of heat shock, osmotic stress, oxidative stress, and hypoxia/reoxygenation injury, as well as ischemic reperfusion injury. Numerous mechanisms that appear to underpin O-GlcNAc-mediated survival include changes in chaperone levels, impacts on the unfolded protein response and integrated stress response, improvements in mitochondrial function, and reduced protein aggregation. Here, we discuss the points at which O-GlcNAc is integrated into the cellular stress response, focusing on the roles it plays in the cardiovascular system and in neurodegeneration.
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Fernandes, Ana Clara, Valerie Uytterhoeven, Sabine Kuenen, Yu-Chun Wang, Jan R. Slabbaert, Jef Swerts, Jaroslaw Kasprowicz, Stein Aerts et Patrik Verstreken. « Reduced synaptic vesicle protein degradation at lysosomes curbs TBC1D24/sky-induced neurodegeneration ». Journal of Cell Biology 207, no 4 (24 novembre 2014) : 453–62. http://dx.doi.org/10.1083/jcb.201406026.
Texte intégralRésumé :
Synaptic demise and accumulation of dysfunctional proteins are thought of as common features in neurodegeneration. However, the mechanisms by which synaptic proteins turn over remain elusive. In this paper, we study Drosophila melanogaster lacking active TBC1D24/Skywalker (Sky), a protein that in humans causes severe neurodegeneration, epilepsy, and DOOR (deafness, onychdystrophy, osteodystrophy, and mental retardation) syndrome, and identify endosome-to-lysosome trafficking as a mechanism for degradation of synaptic vesicle-associated proteins. In fly sky mutants, synaptic vesicles traveled excessively to endosomes. Using chimeric fluorescent timers, we show that synaptic vesicle-associated proteins were younger on average, suggesting that older proteins are more efficiently degraded. Using a genetic screen, we find that reducing endosomal-to-lysosomal trafficking, controlled by the homotypic fusion and vacuole protein sorting (HOPS) complex, rescued the neurotransmission and neurodegeneration defects in sky mutants. Consistently, synaptic vesicle proteins were older in HOPS complex mutants, and these mutants also showed reduced neurotransmission. Our findings define a mechanism in which synaptic transmission is facilitated by efficient protein turnover at lysosomes and identify a potential strategy to suppress defects arising from TBC1D24 mutations in humans.
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Rao, D. S., et K. J. McCracken. « Energy : protein interactions in growing boars of high genetic potential for lean growth. 2. Effects on chemical composition of gain and whole-body protein turn-over ». Animal Science 54, no 1 (février 1992) : 83–93. http://dx.doi.org/10.1017/s0003356100020602.
Texte intégralRésumé :
AbstractThe effect of reducing energy intake within the practical range or reducing energy intake without reducing protein intake on chemical composition of gain, whole-body protein turn-over and energy metabolism was studied between 33 and 90 kg live weight with seven replicates of five littermate boar Landrace pigs. Three levels of food intake (ad libitum, 0·90 and 0·80 ad libitum) were used and the dietary protein contents ranged from 250 to 312 g crude protein (CP) per kg dry matter (DM) to equalize protein intake with reduced food intake. All the diets were of similar amino acid composition and were offered twice daily as pellets. There was no effect of dietary treatment on the DM, CP and fat contents (g/kg) of the empty body (EB), but fat content and fat: protein ratio in EB tended to decrease with reduction of food intake or energy intake. The relationship between energy intake and protein deposition was linear and the mean maximum protein retention was 187 g/day. Retention of DM (P < 0·001), protein (P < 0·001), fat (P < 0·001), energy (P < 0·001) and ash (P < 0·01) decreased linearly with reducing food intake or energy intake. The calculated residual heat production was 0·604 MJ metabolizable energy per kg M0·75 per day. The dietary treatments had no effects on composition of longissimus dorsi, fillet, liver, kidney, backfat or kidney fat. The nitrogen flux, nitrogen synthesis and breakdown tended to decrease with reduction in food intake or energy intake though the effects were not statistically significant. Nitrogen accretion decreased significantly (P < 0·05).
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Green, D. M., et C. T. Whittemore. « Architecture of a harmonized model of the growing pig for the determination of dietary net energy and protein requirements and of excretions into the environment (IMS Pig) ». Animal Science 77, no 1 (avril 2003) : 113–26. http://dx.doi.org/10.1017/s1357729800053716.
Texte intégralRésumé :
AbstractThe model incorporates, amongst its novel components, variable efficiency coefficients in the simulation of the responses of growing pigs to nutrient inputs, and thereby increases the accuracy and efficacy of control of feeding and nitrate excretion. The model determines (rather than is presented with) net energy and required amino acid level and balance. The estimation of protein turn-over as a function of rate of protein retention, protein mass and the maturity of the pig was found to be central to both the energy (ATP) and protein economy. Protein turn-over varied from around 0·14 to 0·08 of the protein mass depending upon the size of the pig. Efficiencies of energy yield from lipid, starch (and sugar), protein and (fibre-derived) volatile fatty acids were calculated to be 0·98, 0·86, 0·56 and 0·58 for ATP production and 0·90, 0·70, 0·50, and 0·44 for lipid retention, respectively. The maximum efficiency of use of ileal digestible amino acids was determined as around 0·85. The energy cost of protein synthesis was equivalent to 4·2 MJ metabolizable energy (ME) per kg, and the efficiency of use of ME for protein retention varied from 0·55 to 0·40 depending on the protein mass of the pig. The components of the model and the biochemical drivers are described in detail, and proof of principle of the main elements is presented. The model is different in its architecture to other published simulation models, and is considered to add to the present knowledge base in this discipline.
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Prelesnik, Jesse L., Robert G. Alberstein, Shuai Zhang, Harley Pyles, David Baker, Jim Pfaendtner, James J. De Yoreo, F. Akif Tezcan, Richard C. Remsing et Christopher J. Mundy. « Ion-dependent protein–surface interactions from intrinsic solvent response ». Proceedings of the National Academy of Sciences 118, no 26 (25 juin 2021) : e2025121118. http://dx.doi.org/10.1073/pnas.2025121118.
Texte intégralRésumé :
The phyllosilicate mineral muscovite mica is widely used as a surface template for the patterning of macromolecules, yet a molecular understanding of its surface chemistry under varying solution conditions, required to predict and control the self-assembly of adsorbed species, is lacking. We utilize all-atom molecular dynamics simulations in conjunction with an electrostatic analysis based in local molecular field theory that affords a clean separation of long-range and short-range electrostatics. Using water polarization response as a measure of the electric fields that arise from patterned, surface-bound ions that direct the adsorption of charged macromolecules, we apply a Landau theory of forces induced by asymmetrically polarized surfaces to compute protein–surface interactions for two muscovite-binding proteins (DHR10-mica6 and C98RhuA). Comparison of the pressure between surface and protein in high-concentration KCl and NaCl aqueous solutions reveals ion-specific differences in far-field protein–surface interactions, neatly capturing the ability of ions to modulate the surface charge of muscovite that in turn selectively attracts one binding face of each protein over all others.
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Toyama, Brandon H., Rafael Arrojo e Drigo, Varda Lev-Ram, Ranjan Ramachandra, Thomas J. Deerinck, Claude Lechene, Mark H. Ellisman et Martin W. Hetzer. « Visualization of long-lived proteins reveals age mosaicism within nuclei of postmitotic cells ». Journal of Cell Biology 218, no 2 (14 décembre 2018) : 433–44. http://dx.doi.org/10.1083/jcb.201809123.
Texte intégralRésumé :
Many adult tissues contain postmitotic cells as old as the host organism. The only organelle that does not turn over in these cells is the nucleus, and its maintenance represents a formidable challenge, as it harbors regulatory proteins that persist throughout adulthood. Here we developed strategies to visualize two classes of such long-lived proteins, histones and nucleoporins, to understand the function of protein longevity in nuclear maintenance. Genome-wide mapping of histones revealed specific enrichment of long-lived variants at silent gene loci. Interestingly, nuclear pores are maintained by piecemeal replacement of subunits, resulting in mosaic complexes composed of polypeptides with vastly different ages. In contrast, nondividing quiescent cells remove old nuclear pores in an ESCRT-dependent manner. Our findings reveal distinct molecular strategies of nuclear maintenance, linking lifelong protein persistence to gene regulation and nuclear integrity.
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Gueudré, Thomas, Carlo Baldassi, Marco Zamparo, Martin Weigt et Andrea Pagnani. « Simultaneous identification of specifically interacting paralogs and interprotein contacts by direct coupling analysis ». Proceedings of the National Academy of Sciences 113, no 43 (11 octobre 2016) : 12186–91. http://dx.doi.org/10.1073/pnas.1607570113.
Texte intégralRésumé :
Understanding protein−protein interactions is central to our understanding of almost all complex biological processes. Computational tools exploiting rapidly growing genomic databases to characterize protein−protein interactions are urgently needed. Such methods should connect multiple scales from evolutionary conserved interactions between families of homologous proteins, over the identification of specifically interacting proteins in the case of multiple paralogs inside a species, down to the prediction of residues being in physical contact across interaction interfaces. Statistical inference methods detecting residue−residue coevolution have recently triggered considerable progress in using sequence data for quaternary protein structure prediction; they require, however, large joint alignments of homologous protein pairs known to interact. The generation of such alignments is a complex computational task on its own; application of coevolutionary modeling has, in turn, been restricted to proteins without paralogs, or to bacterial systems with the corresponding coding genes being colocalized in operons. Here we show that the direct coupling analysis of residue coevolution can be extended to connect the different scales, and simultaneously to match interacting paralogs, to identify interprotein residue−residue contacts and to discriminate interacting from noninteracting families in a multiprotein system. Our results extend the potential applications of coevolutionary analysis far beyond cases treatable so far.
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Sainz, R. D., et J. E. Wolff. « Evaluation of hypotheses regarding mechanisms of action of growth promotants and repartitioning agents using a simulation model of lamb metabolism and growth ». Animal Science 51, no 3 (décembre 1990) : 551–58. http://dx.doi.org/10.1017/s0003356100012587.
Texte intégralRésumé :
ABSTRACTResponses of lambs to cimaterol (CIM), diethylstylbestrol (DES) and ovine growth hormone (GH) were examined using a mechanistic model of growing lamb metabolism. All three compounds increase growth of lean tissue (protein) and decrease fat gain, although the magnitudes of these responses vary. Our working hypothesis was that observed changes in nutrient partition between lean and fat gain were caused by alteration of rate constants for turn-over of muscle protein and fat. Individual experiments were simulated whilst varying values of the protein degradation constant (Kprolein) and Vmax for lipolysis (Kfat). Optimal parameter values were found by minimizing residual errors, calculated as the deviations of model predictions from experimental values for carcass protein and fat. Fitted values of Kfat and Kprotein (expressed as proportions of controls) for each simulation were: CIM (grazing), 1·20 (s.d. 0·05) and 0·86 (s.d. 0·025); CIM (pellet-fed), 1·11 (s.d. 0·115) and 0·87 (s.d. 0·032); DES, 1·33 (s.d. 0·111) and 0·94 (s.d. 0·024); GH, 1·77 (s.d. 0·139) and 0·97 (s.d. 0·025) respectively. These results demonstrate that different mechanisms may be responsible for the changes in carcass composition due to 3-adrenergic agonists, anabolic steroids and growth hormone. CIM probably exerts its effects via changes in protein and fat metabolism, whereas DES and GH appear to act mainly through changes in adipose tissue, with little or no effect on the rate constant for protein turn-over. Carcass composition is less sensitive to manipulation of adipose tissue metabolism than to changes in muscle protein metabolism.
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Goulet, O., S. De Potter, H. Rongier, JJ Robert, C. Ricour et D. Darmaun. « EFFECT OF GRADED NITROGEN INTAKES ON WHOLE BODY PROTEIN TURN OVER MEASURED WITH C-LEUCINE IN ADOLESCENTS ON PARENTERAL NUTRITION (PN) ». Journal of Pediatric Gastroenterology and Nutrition 13, no 3 (octobre 1991) : 331. http://dx.doi.org/10.1097/00005176-199110000-00107.
Texte intégral
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Powers, Kathleen. « The Prion as Nature’s Undead ». Qui Parle 31, no 1 (1 juin 2022) : 109–42. http://dx.doi.org/10.1215/10418385-9669514.
Texte intégralRésumé :
Abstract The prion is a self-replicating protein that infects the central nervous system. This essay applies Georges Canguilhem’s criterion for life, biological normativity, to the prion for the purpose of arguing that the existence of the prion within living systems requires attention to how biological matter uses space. Without the involvement of DNA, the prion protein is physically capable of transforming nonprion proteins into prion proteins—a capacity afforded by the specific characteristics of the energy landscape it propagates within, which in turn is determined by the specific arrangement of atoms in its molecular architecture. Like a hammer that is a mirror, the prion compresses and folds surrounding proteins, making its environment identical to itself. This essay studies how information exchange occurs for the prion for the purpose of arguing for a philosophy of biology premised on the analysis of space with attention to form over the analysis of language with attention to genetic code.
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Campbell, Kevin, et Lukasz Kurgan. « Sequence-Only Based Prediction of β -Turn Location and Type Using Collocation of Amino Acid Pairs ». Open Bioinformatics Journal 2, no 1 (6 août 2008) : 37–49. http://dx.doi.org/10.2174/1875036200802010037.
Texte intégralRésumé :
Development of accurate β-turn (beta-turn) type prediction methods would contribute towards the prediction of the tertiary protein structure and would provide useful insights/inputs for the fold recognition and drug design. Only one existing sequence-only method is available for the prediction of beta-turn types (for type I and II) for the entire protein chains, while the proposed method allows for prediction of type I, II, IV, VII, and non-specific (NS) beta-turns, filling in the gap. The proposed predictor, which is based solely on protein sequence, is shown to provide similar performance to other sequence-only methods for prediction of beta-turns and beta-turn types. The main advantage of the proposed method is simplicity and interpretability of the underlying model. We developed novel sequence-based features that allow identifying beta-turns types and differentiating them from non-beta-turns. The features, which are based on tetrapeptides (entire beta-turns) rather than a window centered over the predicted residues as in the case of recent competing methods, provide a more biologically sound model. They include 12 features based on collocation of amino acid pairs, focusing on amino acids (Gly, Asp, and Asn) that are known to be predisposed to form beta-turns. At the same time, our model also includes features that are geared towards exclusion of non-beta-turns, which are based on amino acids known to be strongly detrimental to formation of beta-turns (Met, Ile, Leu, and Val).
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Ilina, Tatiana V., Zhaoyong Xi, Teresa Brosenitsch, Nicolas Sluis-Cremer et Rieko Ishima. « Large Multidomain Protein NMR : HIV-1 Reverse Transcriptase Precursor in Solution ». International Journal of Molecular Sciences 21, no 24 (15 décembre 2020) : 9545. http://dx.doi.org/10.3390/ijms21249545.
Texte intégralRésumé :
NMR studies of large proteins, over 100 kDa, in solution are technically challenging and, therefore, of considerable interest in the biophysics field. The challenge arises because the molecular tumbling of a protein in solution considerably slows as molecular mass increases, reducing the ability to detect resonances. In fact, the typical 1H-13C or 1H-15N correlation spectrum of a large protein, using a 13C- or 15N-uniformly labeled protein, shows severe line-broadening and signal overlap. Selective isotope labeling of methyl groups is a useful strategy to reduce these issues, however, the reduction in the number of signals that goes hand-in-hand with such a strategy is, in turn, disadvantageous for characterizing the overall features of the protein. When domain motion exists in large proteins, the domain motion differently affects backbone amide signals and methyl groups. Thus, the use of multiple NMR probes, such as 1H, 19F, 13C, and 15N, is ideal to gain overall structural or dynamical information for large proteins. We discuss the utility of observing different NMR nuclei when characterizing a large protein, namely, the 66 kDa multi-domain HIV-1 reverse transcriptase that forms a homodimer in solution. Importantly, we present a biophysical approach, complemented by biochemical assays, to understand not only the homodimer, p66/p66, but also the conformational changes that contribute to its maturation to a heterodimer, p66/p51, upon HIV-1 protease cleavage.
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Barber, J. R., et I. M. Verma. « Modification of fos proteins : phosphorylation of c-fos, but not v-fos, is stimulated by 12-tetradecanoyl-phorbol-13-acetate and serum ». Molecular and Cellular Biology 7, no 6 (juin 1987) : 2201–11. http://dx.doi.org/10.1128/mcb.7.6.2201-2211.1987.
Texte intégralRésumé :
We have investigated the covalent modification of the proteins encoded by the murine fos proto-oncogene (c-fos) and that of the corresponding gene product of FBJ murine osteosarcoma virus (v-fos). Both proteins are posttranslationally processed in the cell, resulting in forms with lower electrophoretic mobilities than that of the initial translation product on sodium dodecyl sulfate-polyacrylamide gels. Treatment with alkaline phosphatase indicates that most, if not all, of this electrophoretic shift is due to phosphoesterification of both proteins. These phosphoryl groups stoichiometrically modify the v-fos and c-fos proteins on serine residues and turn over rapidly in vivo in the presence of protein kinase inhibitors (half-life, less than 15 min). Direct quantitative comparison of steady-state labeling studies with L-[35S]methionine and [32P]phosphate reveals that the c-fos protein is four- to fivefold more highly phosphorylated than the v-fos protein is. Comparison of tryptic fragments from [32P]phosphate-labeled proteins indicates that although the two proteins have several tryptic phosphopeptides in common, the c-fos protein contains unique major tryptic phosphopeptides that the v-fos protein lacks. These unique sites of c-fos phosphorylation have been tentatively localized to the carboxy-terminal 20 amino acid residues of the protein. Phosphorylation of the c-fos protein, but not the v-fos protein, can be stimulated at least fivefold in vivo by the addition of either 12-tetradecanoyl-phorbol-13-acetate or serum. This increase in the steady-state degree of phosphorylation of c-fos appears to be independent of protein kinase C since phosphorylation is Ca2+ and diacylglycerol independent. The possible role of phosphorylation of these proteins in cellular transformation is discussed.
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Barber, J. R., et I. M. Verma. « Modification of fos proteins : phosphorylation of c-fos, but not v-fos, is stimulated by 12-tetradecanoyl-phorbol-13-acetate and serum. » Molecular and Cellular Biology 7, no 6 (juin 1987) : 2201–11. http://dx.doi.org/10.1128/mcb.7.6.2201.
Texte intégralRésumé :
We have investigated the covalent modification of the proteins encoded by the murine fos proto-oncogene (c-fos) and that of the corresponding gene product of FBJ murine osteosarcoma virus (v-fos). Both proteins are posttranslationally processed in the cell, resulting in forms with lower electrophoretic mobilities than that of the initial translation product on sodium dodecyl sulfate-polyacrylamide gels. Treatment with alkaline phosphatase indicates that most, if not all, of this electrophoretic shift is due to phosphoesterification of both proteins. These phosphoryl groups stoichiometrically modify the v-fos and c-fos proteins on serine residues and turn over rapidly in vivo in the presence of protein kinase inhibitors (half-life, less than 15 min). Direct quantitative comparison of steady-state labeling studies with L-[35S]methionine and [32P]phosphate reveals that the c-fos protein is four- to fivefold more highly phosphorylated than the v-fos protein is. Comparison of tryptic fragments from [32P]phosphate-labeled proteins indicates that although the two proteins have several tryptic phosphopeptides in common, the c-fos protein contains unique major tryptic phosphopeptides that the v-fos protein lacks. These unique sites of c-fos phosphorylation have been tentatively localized to the carboxy-terminal 20 amino acid residues of the protein. Phosphorylation of the c-fos protein, but not the v-fos protein, can be stimulated at least fivefold in vivo by the addition of either 12-tetradecanoyl-phorbol-13-acetate or serum. This increase in the steady-state degree of phosphorylation of c-fos appears to be independent of protein kinase C since phosphorylation is Ca2+ and diacylglycerol independent. The possible role of phosphorylation of these proteins in cellular transformation is discussed.
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Balasubramanian, Anuradha, Monica Markovski, Joel R. Hoskins, Shannon M. Doyle et Sue Wickner. « Hsp90 of E. coli modulates assembly of FtsZ, the bacterial tubulin homolog ». Proceedings of the National Academy of Sciences 116, no 25 (3 juin 2019) : 12285–94. http://dx.doi.org/10.1073/pnas.1904014116.
Texte intégralRésumé :
Heat shock protein 90 (Hsp90) is a highly conserved molecular chaperone involved in ATP-dependent client protein remodeling and activation. It also functions as a protein holdase, binding and stabilizing clients in an ATP-independent process. Hsp90 remodels over 300 client proteins and is essential for cell survival in eukaryotes. In bacteria, Hsp90 is a highly abundant protein, although very few clients have been identified and it is not essential for growth in many bacterial species. We previously demonstrated that in Escherichia coli, Hsp90 causes cell filamentation when expressed at high levels. Here, we have explored the cause of filamentation and identified a potentially important client of E. coli Hsp90 (Hsp90Ec), FtsZ. We observed that FtsZ, a bacterial tubulin homolog essential for cell division, fails to assemble into FtsZ rings (divisomes) in cells overexpressing Hsp90Ec. Additionally, Hsp90Ec interacts with FtsZ and inhibits polymerization of FtsZ in vitro, in an ATP-independent holding reaction. The FtsZ–Hsp90Ec interaction involves residues in the client-binding region of Hsp90Ec and in the C-terminal tail of FtsZ, where many cell-division proteins and regulators interact. We observed that E. coli deleted for the Hsp90Ec gene htpG turn over FtsZ more rapidly than wild-type cells. Additionally, the length of ΔhtpG cells is reduced compared to wild-type cells. Altogether, these results suggest that Hsp90Ec is a modulator of cell division, and imply that the polypeptide-holding function of Hsp90 may be a biologically important chaperone activity.
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SRIHARI, SRIGANESH, et HON WAI LEONG. « A SURVEY OF COMPUTATIONAL METHODS FOR PROTEIN COMPLEX PREDICTION FROM PROTEIN INTERACTION NETWORKS ». Journal of Bioinformatics and Computational Biology 11, no 02 (avril 2013) : 1230002. http://dx.doi.org/10.1142/s021972001230002x.
Texte intégralRésumé :
Complexes of physically interacting proteins are one of the fundamental functional units responsible for driving key biological mechanisms within the cell. Their identification is therefore necessary to understand not only complex formation but also the higher level organization of the cell. With the advent of "high-throughput" techniques in molecular biology, significant amount of physical interaction data has been cataloged from organisms such as yeast, which has in turn fueled computational approaches to systematically mine complexes from the network of physical interactions among proteins (PPI network). In this survey, we review, classify and evaluate some of the key computational methods developed till date for the identification of protein complexes from PPI networks. We present two insightful taxonomies that reflect how these methods have evolved over the years toward improving automated complex prediction. We also discuss some open challenges facing accurate reconstruction of complexes, the crucial ones being the presence of high proportion of errors and noise in current high-throughput datasets and some key aspects overlooked by current complex detection methods. We hope this review will not only help to condense the history of computational complex detection for easy reference but also provide valuable insights to drive further research in this area.
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Solomon, David A., M. Cristina Cardoso et Erik S. Knudsen. « Dynamic targeting of the replication machinery to sites of DNA damage ». Journal of Cell Biology 166, no 4 (16 août 2004) : 455–63. http://dx.doi.org/10.1083/jcb.200312048.
Texte intégralRésumé :
Components of the DNA replication machinery localize into discrete subnuclear foci after DNA damage, where they play requisite functions in repair processes. Here, we find that the replication factors proliferating cell nuclear antigen (PCNA) and RPAp34 dynamically exchange at these repair foci with discrete kinetics, and this behavior is distinct from kinetics during DNA replication. Posttranslational modification is hypothesized to target specific proteins for repair, and we find that accumulation and stability of PCNA at sites of damage requires monoubiquitination. Contrary to the popular notion that phosphorylation on the NH2 terminus of RPAp34 directs the protein for repair, we demonstrate that phosphorylation by DNA-dependent protein kinase enhances RPAp34 turnover at repair foci. Together, these findings support a dynamic exchange model in which multiple repair factors regulated by specific modifications have access to and rapidly turn over at sites of DNA damage.
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Höhn, Annika, Antonella Tramutola et Roberta Cascella. « Proteostasis Failure in Neurodegenerative Diseases : Focus on Oxidative Stress ». Oxidative Medicine and Cellular Longevity 2020 (27 mars 2020) : 1–21. http://dx.doi.org/10.1155/2020/5497046.
Texte intégralRésumé :
Protein homeostasis or proteostasis is an essential balance of cellular protein levels mediated through an extensive network of biochemical pathways that regulate different steps of the protein quality control, from the synthesis to the degradation. All proteins in a cell continuously turn over, contributing to development, differentiation, and aging. Due to the multiple interactions and connections of proteostasis pathways, exposure to stress conditions may cause various types of protein damage, altering cellular homeostasis and disrupting the entire network with additional cellular stress. Furthermore, protein misfolding and/or alterations during protein synthesis results in inactive or toxic proteins, which may overload the degradation mechanisms. The maintenance of a balanced proteome, preventing the formation of impaired proteins, is accomplished by two major catabolic routes: the ubiquitin proteasomal system (UPS) and the autophagy-lysosomal system. The proteostasis network is particularly important in nondividing, long-lived cells, such as neurons, as its failure is implicated with the development of neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis. These neurological disorders share common risk factors such as aging, oxidative stress, environmental stress, and protein dysfunction, all of which alter cellular proteostasis, suggesting that general mechanisms controlling proteostasis may underlay the etiology of these diseases. In this review, we describe the major pathways of cellular proteostasis and discuss how their disruption contributes to the onset and progression of neurodegenerative diseases, focusing on the role of oxidative stress.
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Loyer, P., J. H. Trembley, J. M. Lahti et V. J. Kidd. « The RNP protein, RNPS1, associates with specific isoforms of the p34cdc2-related PITSLRE protein kinase in vivo ». Journal of Cell Science 111, no 11 (1 juin 1998) : 1495–506. http://dx.doi.org/10.1242/jcs.111.11.1495.
Texte intégralRésumé :
The PITSLRE protein kinases are members of the p34cdc2 superfamily, with >20 different isoforms expressed from two linked genes in humans. PITSLRE homologues have been identified in mouse, chicken, Drosophila, Xenopus, and possibly Plasmodium falciparum, suggesting that their function may be well conserved. A possible role for a caspase processed PITSLRE isoform has been suggested by studies of Fas- and TNF-induced cell death. However, the function of these kinases in proliferating cells is still unknown. Here we demonstrate that the 110 kDa PITSLRE isoforms (p110) are localized to both the nucleoplasm and nuclear speckles, and that these isoforms specifically interact in vitro and in vivo with the RNA-binding protein RNPS1. RNPS1 is also localized to nuclear speckles, and its over expression disrupts normal nuclear speckle organization by causing the aggregation of many nuclear speckles into approximately 6 ‘mega’ speckles. This type of nuclear speckle aggregation closely resembles what occurs when cells are treated with several transcriptional inhibitors. These data indicate that the PITSLRE p110 isoforms interact with RNPS1 in vivo, and that these proteins may in turn influence some aspect of transcriptional and/or splicing regulation.
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Silverman, J. A., J. Mehta, S. Brocher et J. S. Amenta. « Analytical errors in measuring radioactivity in cell proteins and their effect on estimates of protein turnover in L cells ». Biochemical Journal 226, no 2 (1 mars 1985) : 361–68. http://dx.doi.org/10.1042/bj2260361.
Texte intégralRésumé :
Previous studies from this laboratory on protein turnover in 3H-labelled L-cell cultures have shown recovery of total 3H at the end of a 3-day experiment to be always significantly in excess of the 3H recovered at the beginning of the experiment. In this study we have critically reviewed a number of possible sources for this error in measuring radioactivity in cell proteins. 3H-labelled proteins, when dissolved in 0.3 M-NaOH and counted for radioactivity in a liquid-scintillation spectrometer, showed losses of 30-40% of the radioactivity; neither external or internal standardization compensated for this loss. Hydrolysis of these proteins with either Pronase or concentrated HCl significantly increased the measured radioactivity. In addition, approx. 5-10% of the cell protein is left on the plastic culture dish when cells are recovered in phosphate-buffered saline. To aggravate this latter loss further, this surface-adherent protein, after pulse labelling, contains proteins of high radioactivity that turn over rapidly and make a major contribution to the accumulating radioactivity in the medium. These combined errors can account for up to 60% of the total radioactivity in the cell culture. Similar analytical errors have been found in studies of other cell cultures. The effect of these analytical errors on estimates of protein turnover in cell cultures is discussed.
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Tan, Maxine H., Sarah R. Smith, Kim K. Hixson, Justin Tan, James K. McCarthy, Adam B. Kustka et Andrew E. Allen. « The Importance of Protein Phosphorylation for Signaling and Metabolism in Response to Diel Light Cycling and Nutrient Availability in a Marine Diatom ». Biology 9, no 7 (6 juillet 2020) : 155. http://dx.doi.org/10.3390/biology9070155.
Texte intégralRésumé :
Diatoms are major contributors to global primary production and their populations in the modern oceans are affected by availability of iron, nitrogen, phosphate, silica, and other trace metals, vitamins, and infochemicals. However, little is known about the role of phosphorylation in diatoms and its role in regulation and signaling. We report a total of 2759 phosphorylation sites on 1502 proteins detected in Phaeodactylum tricornutum. Conditionally phosphorylated peptides were detected at low iron (n = 108), during the diel cycle (n = 149), and due to nitrogen availability (n = 137). Through a multi-omic comparison of transcript, protein, phosphorylation, and protein homology, we identify numerous proteins and key cellular processes that are likely under control of phospho-regulation. We show that phosphorylation regulates: (1) carbon retrenchment and reallocation during growth under low iron, (2) carbon flux towards lipid biosynthesis after the lights turn on, (3) coordination of transcription and translation over the diel cycle and (4) in response to nitrogen depletion. We also uncover phosphorylation sites for proteins that play major roles in diatom Fe sensing and utilization, including flavodoxin and phytotransferrin (ISIP2A), as well as identify phospho-regulated stress proteins and kinases. These findings provide much needed insight into the roles of protein phosphorylation in diel cycling and nutrient sensing in diatoms.
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Gunter, Stacey, et Corey A. Moffet. « 39 Thoughts on the energetic efficiency of grazing cattle ». Journal of Animal Science 97, Supplement_1 (juillet 2019) : 69. http://dx.doi.org/10.1093/jas/skz053.156.
Texte intégralRésumé :
Abstract Energetic efficiency of cattle is a significant issue in the beef industry. Ruminant nutritionists have made strides in improving production efficiency, but we still see significant variation among individuals. A popular method for evaluating the cattle efficiency is selection based on residual feed intake. This method has some limitations because of mounting evidence that it has a genotype x environment interaction. Individuals deemed most efficient being fed in confinement are not most efficient when their environment is grazing. Hence, cattle efficiencies need to be evaluated in appropriate environments. Because it is impossible to directly measure DMI by grazing cattle, we need to develop proxies to assess the animal’s efficiency. By using experimental methods such as breath cloud analysis to provide individual estimates of total heat of production and known constants for retained energy in BW gain, we can calculate ME energy intake. However, we still lack the ability to measure DMI without the true digestibility of the grazed diet. The greatest energy expenditure is basal metabolism and if we are to decrease it, we will need to examine their body composition and protein-turnover rates. The rates of protein and fat deposition in the carcass affects an animal’s efficiency and ADG chiefly because of the higher energy density of fat. However, with great protein deposition, there also is a higher ME requirement for its maintenance because of the high protein turn-over rate. Energy expensed for protein turnover is approximately 23% of the total energy intake by average cattle. Management that decreases body protein turn-over rate probably would result in a decreased basal metabolism. The research needed to truly improve the energetic efficiency of grazing cattle will be time consuming and expensive, but for progress to be made it will be required.
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Ginting, Andi Raga, Rudy Hidayat, Sumariyono Sumariyono et Sukamto Koesnoe. « Role of Secreted Frizzled-Related Protein 1 and Tumor Necrosis Factor-α (TNF-α) in Bone Loss of Patients with Rheumatoid Arthritis ». International Journal of Rheumatology 2020 (1 mars 2020) : 1–7. http://dx.doi.org/10.1155/2020/9149762.
Texte intégralRésumé :
Bone loss is one of the emerging extra-articular manifestations of rheumatoid arthritis. TNF-α is the main inflammatory cytokine that can directly increase bone resorption. However, its role in bone formation is still unknown, especially related to secreted frizzled-related protein 1 (SFRP-1), an osteoblast inhibitor. This study examines the correlation between TNF-α and SFRP-1, with a bone turn over marker (CTX and P1NP). This is a cross-sectional study with 38 subjects of premenopausal female patients with RA. This study found that 60.6% of the patients were in remission or low disease activity. The median of TNF-α was 10.6 pg/mL, mean of SFRP-1 was 9.29 ng/mL, mean of CTX was 2.74 ng/mL, and the median of P1NP was 34.04 pg/ml. There is positive correlation between TNF-α and P1NP (r=0.363, p=0.026), also between SFRP-1 and P1NP (r=0.341; p=0.036). A low level of TNF-𝛼, high level of SFRP-1, high level of CTX, and low level of P1NP in this study indicate a high bone turn over process, with dominant resorption activity in premenopausal female patients with RA.
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Premrov Bajuk, Blanka, Petra Zrimšek, Maja Zakošek Pipan, Bruno Tilocca, Alessio Soggiu, Luigi Bonizzi et Paola Roncada. « Proteomic Analysis of Fresh and Liquid-Stored Boar Spermatozoa ». Animals 10, no 4 (26 mars 2020) : 553. http://dx.doi.org/10.3390/ani10040553.
Texte intégralRésumé :
In this study comparative proteomics was used to define changes in the expression of the spermatozoa proteins during liquid storage. Semen from eight boars was analyzed on the day of collection and after liquid preservation at 15–17 °C for three days. Sperm parameters (concentration, motility, morphology, vitality) and percentage of non-capacitated and acrosomal-reacted spermatozoa were determined. Sperm proteins were extracted and separated by two-dimensional sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and proteomic profiles were computationally compared to highlight differentially expressed protein spots that were, in turn, identified by mass spectrometry. The intensities of four spots were significantly different between fresh and liquid stored sperm. Namely: ATP citrate lyase, chaperonin containing T-complex polypeptide 1 (TCP1) subunit ε and probable phospholipid-transporting ATP-ase were over-expressed in liquid stored sperm, whereas cytosolic non-specific dipeptidase was over-expressed in fresh sperm. These differentially expressed proteins could be used as plausible biomarkers for the evaluation of boar semen quality and spermatozoa survival after liquid storage and could help to address problems associated with sperm preservation.
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Pereira, Ricardo N., et Rui M. Rodrigues. « Emergent Proteins-Based Structures—Prospects towards Sustainable Nutrition and Functionality ». Gels 7, no 4 (1 octobre 2021) : 161. http://dx.doi.org/10.3390/gels7040161.
Texte intégralRésumé :
The increased pressure over soils imposed by the need for agricultural expansion and food production requires development of sustainable and smart strategies for the efficient use of resources and food nutrients. In accordance with worldwide transformative polices, it is crucial to design sustainable systems for food production aimed at reducing environmental impact, contributing to biodiversity preservation, and leveraging a bioeconomy that supports circular byproduct management. Research on the use of emergent protein sources to develop value-added foods and biomaterials is in its infancy. This review intends to summarize recent research dealing with technological functionality of underused protein fractions, recovered from microbial biomass and food waste sources, addressing their potential applications but also bottlenecks. Protein-based materials from dairy byproducts and microalgae biomass gather promising prospects of use related to their techno-functional properties. However, a balance between yield and functionality is needed to turn this approach profitable on an industrial scale basis. In this context, downstream processing should be strategically used and properly integrated. Food solutions based on microbial proteins will expand in forthcoming years, bringing the opportunity to finetune development of novel protein-based biomaterials.