Готові списки джерел за темами / Homodimers

Добірка наукової літератури з теми "Homodimers"

Автор: Grafiati
Опубліковано: 10 грудня 2022
Оновлено: 28 січня 2023

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Статті в журналах з теми "Homodimers"

1

Krause, Jean-Michel, Peter Berger, Jordi Roig, Vinod Singh та Wolfgang E. Merz. "Rapid Maturation of Glycoprotein Hormone Free α-Subunit (GPHα) and GPHαα Homodimers". Molecular Endocrinology 21, № 10 (1 жовтня 2007): 2551–64. http://dx.doi.org/10.1210/me.2007-0051.

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Abstract The dynamics of glycoprotein hormone α-subunit (GPHα) maturation and GPHαα homodimer formation were studied in presence (JEG-3 choriocarcinoma cells) and absence (HeLa cells) of hCGβ. In both cases, the major initially occurring GPHα variant in [35S]Met/Cys-labeled cells carried two N-glycans (Mr app = 22 kDa). Moreover, a mono-N-glycosylated in vivo association-incompetent GPHα variant (Mr app = 18 kDa) was observed. In JEG-3 cells the early 22-kDa GPHα either associated with hCGβ, or showed self-association to yield GPHαα homodimers, or was later converted into heavily glycosylated large free GPHα (Mr app = 24 kDa). Micro-preparative isolation of intracellular GPHαα homodimers of JEG-3 cells and their conversion by reduction revealed that they consisted of 22-kDa GPHα monomers and not of large free GPHα. In HeLa cells, the large free GPHα variant was not observed, whereas GPHαα homodimers were present. Intracellularly, early GPHαα homodimers (35 kDa) and late variants (JEG-3: 44 kDa, HeLa: 39 kDa) were found. Both cell types secreted 45 kDa GPHαα homodimers. Large free GPHα and GPHαα homodimers were more rapidly sialylated than hCG αβ-heterodimers indicating a sequestration mechanism in the secretory pathway. In GPHαα homo- as well as hCG αβ-heterodimers the subunit interaction site, located on loop 2 of GPHα (amino acids 33–42), became immunologically inaccessible indicating similar spatial orientation of GPHα in both types of dimers. The studies demonstrate the formation, in vivo dynamics of GPHαα homodimers, and the pathways of the cellular metabolism of variants of GPHα, monoglycosylated GPHα and large free GPHα.
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2

Hadarovich, A. Y., A. A. Kalinouski, and A. V. Tuzikov. "Protein homodimers structure prediction based on deep neural network." Informatics 17, no. 2 (June 26, 2020): 44–53. http://dx.doi.org/10.37661/1816-0301-2020-17-2-44-53.

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Structural prediction of protein-protein complexes has important application in such domains as modeling of biological processes and drug design. Homodimers (complexes which consist of two identical proteins) are the most common type of protein complexes in nature but there is still no universal algorithm to predict their 3D structures. Experimental techniques to identify the structure of protein complex require enormous amount of time and resources, and each method has its own limitations. Recently Deep Neural Networks allowed to predict structures of individual proteins greatly prevailing in accuracy over other algorithmic approaches. Building on the idea of this approach, we developed an algorithm to model the 3D structure of homodimer based on deep learning. It consists of two major steps: at the first step a protein complex contact map is predicted with the deep convolutional neural network, and the second stage is used to predict 3D structure of homodimer based on obtained contact map and optimization procedure. The use of the neural network in combination with optimization procedure based on gradient descent method allowed to predict structures for protein homodimers. The suggested approach was tested and validated on a dataset of protein homodimers from Protein Data Bank (PDB). The developed procedure could be also used for evaluating protein homodimer models as one of the stages in drug compounds developing.
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3

Geng, Jie, та Malini Raghavan. "CD8αα homodimers function as a coreceptor for KIR3DL1". Proceedings of the National Academy of Sciences 116, № 36 (16 серпня 2019): 17951–56. http://dx.doi.org/10.1073/pnas.1905943116.

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Cluster of differentiation 8 (CD8) is a cell surface glycoprotein, which is expressed as 2 forms, αα homodimer or αβ heterodimer. Peptide-loaded major histocompatibility complex class I (pMHC-I) molecules are major ligands for both forms of CD8. CD8αβ is a coreceptor for the T cell receptor (TCR) and binds to the same cognate pMHC-I as the TCR, thus enabling or augmenting T cell responses. The function of CD8αα homodimers is largely unknown. While CD8αβ heterodimer is expressed exclusively on CD8+ T cells, the CD8αα homodimer is present in subsets of T cells and human natural killer (NK) cells. Here, we report that the CD8αα homodimer functions as a coreceptor for KIR3DL1, an inhibitory receptor of NK cells that is specific for certain MHC-I allotypes. CD8αα enhances binding of pMHC-I to KIR3DL1, increases KIR3DL1 clustering at the immunological synapse, and augments KIR3DL1-mediated inhibition of NK cell activation. Additionally, interactions between pMHC-I and CD8αα homodimers regulate KIR3DL1+ NK cell education. Together, these findings reveal another dimension to the modulation of NK cell activity.
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4

Tajer, Benjamin, James A. Dutko, Shawn C. Little, and Mary C. Mullins. "BMP heterodimers signal via distinct type I receptor class functions." Proceedings of the National Academy of Sciences 118, no. 15 (April 7, 2021): e2017952118. http://dx.doi.org/10.1073/pnas.2017952118.

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Heterodimeric TGF-β ligands outperform homodimers in a variety of developmental, cell culture, and therapeutic contexts; however, the mechanisms underlying this increased potency remain uncharacterized. Here, we use dorsal–ventral axial patterning of the zebrafish embryo to interrogate the BMP2/7 heterodimer signaling mechanism. We demonstrate that differential interactions with BMP antagonists do not account for the reduced signaling ability of homodimers. Instead, we find that while overexpressed BMP2 homodimers can signal, they require two nonredundant type I receptors, one from the Acvr1 subfamily and one from the Bmpr1 subfamily. This implies that all BMP signaling within the zebrafish gastrula, even BMP2 homodimer signaling, requires Acvr1. This is particularly surprising as BMP2 homodimers do not bind Acvr1 in vitro. Furthermore, we find that the roles of the two type I receptors are subfunctionalized within the heterodimer signaling complex, with the kinase activity of Acvr1 being essential, while that of Bmpr1 is not. These results suggest that the potency of the Bmp2/7 heterodimer arises from the ability to recruit both Acvr1 and Bmpr1 into the same signaling complex.
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5

Peng, K.-C., D. Puett, and J. M. Brewer. "Homodimer formation by the individual subunits of bovine lutropin as determined by sedimentation equilibrium." Journal of Molecular Endocrinology 18, no. 3 (June 1997): 259–65. http://dx.doi.org/10.1677/jme.0.0180259.

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ABSTRACT Although differing in their amino acid sequences, the folding patterns of the α and β subunits of human choriogonadotropin are similar in the crystal structure of the HF-treated glycoprotein hormone. Each subunit forms a cystine-knot motif like that found in several growth factors that form homodimers and heterodimers. In order to ascertain if the α and β subunits can self-associate, e.g. to form homodimers, sedimentation equilibrium at various glycoprotein concentrations and temperatures was used to study the subunits of bovine lutropin, which are expected to exhibit conformations like those of the choriogonadotropin subunits. Each subunit was found to form homodimers with Kd values of 0·3 and 0·1 mm for α and β respectively at 37 °C. Self-association was weakly exothermic for α and endothermic for β; entropic factors made a major contribution for each. It is unlikely that homodimer formation of either subunit would be physiologically important, although homodimers may form to some extent intracellularly because of the relatively high concentrations during biosynthesis.
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6

Garton, Michael, Stephen S. MacKinnon, Anatoly Malevanets, and Shoshana J. Wodak. "Interplay of self-association and conformational flexibility in regulating protein function." Philosophical Transactions of the Royal Society B: Biological Sciences 373, no. 1749 (May 7, 2018): 20170190. http://dx.doi.org/10.1098/rstb.2017.0190.

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Many functional roles have been attributed to homodimers, the most common mode of protein self-association, notably in the regulation of enzymes, ion channels, transporters and transcription factors. Here we review findings that offer new insights into the different roles conformational flexibility plays in regulating homodimer function. Intertwined homodimers of two-domain proteins and their related family members display significant conformational flexibility, which translates into concerted motion between structural domains. This flexibility enables the corresponding proteins to regulate function across family members by modulating the spatial positions of key recognition surfaces of individual domains, to either maintain subunit interfaces, alter them or break them altogether, leading to a variety of functional consequences. Many proteins may exist as monomers but carry out their biological function as homodimers or higher-order oligomers. We present early evidence that in such systems homodimer formation primes the protein for its functional role. It does so by inducing elevated mobility in protein regions corresponding to the binding epitopes of functionally important ligands. In some systems this process acts as an allosteric response elicited by the self-association reaction itself. Our analysis furthermore suggests that the induced extra mobility likely facilitates ligand binding through the mechanism of conformational selection. This article is part of a discussion meeting issue ‘Allostery and molecular machines’.
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7

Campbell, Brandon, Marharyta Petukh, Emil Alexov, and Chuan Li. "On the electrostatic properties of homodimeric proteins." Journal of Theoretical and Computational Chemistry 13, no. 03 (May 2014): 1440007. http://dx.doi.org/10.1142/s0219633614400070.

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A large fraction of proteins function as homodimers, but it is not always clear why the dimerization is important for functionality since frequently each monomer possesses a distinctive active site. Recent work (PLoS Computational Biology9(2):e1002924) indicates that homodimerization may be important for forming an electrostatic funnel in the spermine synthase homodimer which guides changed substrates toward the active centers. This prompted us to investigate the electrostatic properties of a large set of homodimeric proteins and resulted in an observation that in a vast majority of the cases the dimerization indeed results in specific electrostatic features, although not necessarily in an electrostatic funnel. It is demonstrated that the electrostatic dipole moment of the dimer is predominantly perpendicular to the axis connecting the centers of the mass of the monomers. In addition, the surface points with highest potential are located in the proximity of the interfacial plane of the homodimeric complexes. These findings indicate that frequent homodimerization provides specific electrostatic features needed for the function of proteins.
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8

Ibrahim, Mahmoud A. A., Rehab R. A. Saeed, Mohammed N. I. Shehata, Muhammad Naeem Ahmed, Ahmed M. Shawky, Manal M. Khowdiary, Eslam B. Elkaeed, Mahmoud E. S. Soliman, and Nayra A. M. Moussa. "Type I–IV Halogen⋯Halogen Interactions: A Comparative Theoretical Study in Halobenzene⋯Halobenzene Homodimers." International Journal of Molecular Sciences 23, no. 6 (March 14, 2022): 3114. http://dx.doi.org/10.3390/ijms23063114.

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In the current study, unexplored type IV halogen⋯halogen interaction was thoroughly elucidated, for the first time, and compared to the well-established types I–III interactions by means of the second-order Møller–Plesset (MP2) method. For this aim, the halobenzene⋯halobenzene homodimers (where halogen = Cl, Br, and I) were designed into four different types, parodying the considered interactions. From the energetic perspective, the preference of scouted homodimers was ascribed to type II interactions (i.e., highest binding energy), whereas the lowest binding energies were discerned in type III interactions. Generally, binding energies of the studied interactions were observed to decline with the decrease in the σ-hole size in the order, C6H5I⋯IC6H5 > C6H5Br⋯BrC6H5 > C6H5Cl⋯ClC6H5 homodimers and the reverse was noticed in the case of type IV interactions. Such peculiar observations were relevant to the ample contributions of negative-belt⋯negative-belt interactions within the C6H5Cl⋯ClC6H5 homodimer. Further, type IV torsional trans → cis interconversion of C6H5X⋯XC6H5 homodimers was investigated to quantify the π⋯π contributions into the total binding energies. Evidently, the energetic features illustrated the amelioration of the considered homodimers (i.e., more negative binding energy) along the prolonged scope of torsional trans → cis interconversion. In turn, these findings outlined the efficiency of the cis configuration over the trans analog. Generally, symmetry-adapted perturbation theory-based energy decomposition analysis (SAPT-EDA) demonstrated the predominance of all the scouted homodimers by the dispersion forces. The obtained results would be beneficial for the omnipresent studies relevant to the applications of halogen bonds in the fields of materials science and crystal engineering.
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9

Bonsor, Daniel A., Sebastian Günther, Robert Beadenkopf, Dorothy Beckett, and Eric J. Sundberg. "Diverse oligomeric states of CEACAM IgV domains." Proceedings of the National Academy of Sciences 112, no. 44 (October 19, 2015): 13561–66. http://dx.doi.org/10.1073/pnas.1509511112.

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Carcinoembryonic antigen-related cell adhesion molecules (CEACAMs) comprise a large family of cell surface adhesion molecules that bind to themselves and other family members to carry out numerous cellular functions, including proliferation, signaling, differentiation, tumor suppression, and survival. They also play diverse and significant roles in immunity and infection. The formation of CEACAM oligomers is caused predominantly by interactions between their N-terminal IgV domains. Although X-ray crystal structures of CEACAM IgV domain homodimers have been described, how CEACAMs form heterodimers or remain monomers is poorly understood. To address this key aspect of CEACAM function, we determined the crystal structures of IgV domains that form a homodimeric CEACAM6 complex, monomeric CEACAM8, and a heterodimeric CEACAM6–CEACAM8 complex. To confirm and quantify these interactions in solution, we used analytical ultracentrifugation to measure the dimerization constants of CEACAM homodimers and isothermal titration calorimetry to determine the thermodynamic parameters and binding affinities of CEACAM heterodimers. We found the CEACAM6–CEACAM8 heterodimeric state to be substantially favored energetically relative to the CEACAM6 homodimer. Our data provide a molecular basis for the adoption of the diverse oligomeric states known to exist for CEACAMs and suggest ways in which CEACAM6 and CEACAM8 regulate the biological functions of one another, as well as of additional CEACAMs with which they interact, both in cis and in trans.
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10

Mou, Yun, Po-Ssu Huang, Fang-Ciao Hsu, Shing-Jong Huang, and Stephen L. Mayo. "Computational design and experimental verification of a symmetric protein homodimer." Proceedings of the National Academy of Sciences 112, no. 34 (August 12, 2015): 10714–19. http://dx.doi.org/10.1073/pnas.1505072112.

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Homodimers are the most common type of protein assembly in nature and have distinct features compared with heterodimers and higher order oligomers. Understanding homodimer interactions at the atomic level is critical both for elucidating their biological mechanisms of action and for accurate modeling of complexes of unknown structure. Computation-based design of novel protein–protein interfaces can serve as a bottom-up method to further our understanding of protein interactions. Previous studies have demonstrated that the de novo design of homodimers can be achieved to atomic-level accuracy by β-strand assembly or through metal-mediated interactions. Here, we report the design and experimental characterization of a α-helix–mediated homodimer with C2 symmetry based on a monomeric Drosophila engrailed homeodomain scaffold. A solution NMR structure shows that the homodimer exhibits parallel helical packing similar to the design model. Because the mutations leading to dimer formation resulted in poor thermostability of the system, design success was facilitated by the introduction of independent thermostabilizing mutations into the scaffold. This two-step design approach, function and stabilization, is likely to be generally applicable, especially if the desired scaffold is of low thermostability.
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Більше джерел

Дисертації з теми "Homodimers"

1

Burnell, David. "Multi-scale modelling of allostery in protein homodimers." Thesis, Durham University, 2015. http://etheses.dur.ac.uk/11055/.

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Allostery is a form of signalling within biomolecules such that ligand binding to a protein affects its activity at a second site. Allostery was described by early models to be driven by structural changes in the protein. However, more recently there has been increasing evidence that dynamics can contribute to or even drive allostery. The protein studied in this thesis, the Catabolite Activator Protein (CAP), is an allosteric protein homodimer that has been shown to exhibit negatively cooperative binding of the ligand cyclic Adenosine Monophosphate (cAMP) to each of its monomers. Interestingly, CAP is a protein whose allostery is believed to be driven by dynamics rather than a conformational change. In this thesis, a number of coarse grained models are employed to investigate this dynamic allostery in CAP. One family of models, termed Super Coarse Grained (SCG) models explore the global properties of the dynamics of the CAP dimer that cause it to exhibit negatively cooperative allostery. It is shown through these models that changes in protein interactions can provide a basis for changing cooperativity. A second family of coarse grained models called Elastic Network Models (ENM) are studied. These are used to show that adjusting the interactions between specific residues can affect cooperative binding of cAMP to CAP. A number of atomistic approaches are also used to study the cAMP-CAP system, including Molecular Dynamics (MD) and Normal Mode Analysis (NMA). The efficacy of using such approaches for studying the thermodynamics of the allostery in CAP is investigated. The motion observed within the protein is also studied closely to identify potential allosteric pathways. X-ray crystallography and Isothermal Titration Calorimetry (ITC) are finally used to investigate how accurately computational methods can describe the cooperative binding of cAMP to CAP. They are also used to try and determine whether the allostery in CAP can be manipulated experimentally without any observed changes to its structure.
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2

Sanders, David A. R. 1968. "Thioredoxin homodimers: Effects of mutation and oxidation on structure and dimer formation." Diss., The University of Arizona, 1998. http://hdl.handle.net/10150/282851.

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Thioredoxins are a family of small redox proteins that mediate a number of cytosolic processes in the cells of all organisms. Human thioredoxin has a number of additional functions, including the apparent stimulation of NF-κB and AP-1 transcriptional activation. It can also be exported out of the cell, where it apparently has additional functions including the ability to stimulate cell growth. The crystal structure of human thioredoxin revealed that the protein can form a homodimer. The dimer contains a disulfide bond between the Cys 73 residues of each monomer, and a novel hydrogen bond between the Asp 60 residue of each monomer that is responsible for the pH dependent behaviour of dimerization. This work was undertaken with two goals. First, three mutant protein with changes in the dimer interface, Asp58 → Ser (D58S), Ala66 → Arg (A66R) and Trp31 → Ala (W31A) were isolated and characterized. The ability of the mutant proteins to form dimers, their activities with respect to the reduction of insulin disulfides and their interaction with thioredoxin reductase were examined. The three mutations affected thioredoxins ability to form dimers: the W31A and A66R mutant proteins formed dimers less well, and the D58S mutant protein lost the pH dependence for dimer formation. Thioredoxin with a D58S mutation behaved very similarly to wild type in the activity assays, while A66R showed a 6-fold increase in K(m) and W31A showed large changes to both K(m) and V(max). From these results I suggest that the dimer interface plays a role in defining the binding site for thioredoxin reductase. The second goal was to examine the role that oxidation of the active site plays in dimerization. Oxidation, which results in structural changes to the dimer interface, also caused thioredoxin to form dimers much less readily. The reduction in dimer formation offers a possible mechanism through which thioredoxin could play a role in signaling oxidative stress. The findings detailed here begin to describe the role that the dimeric form of thioredoxin could play in physiological situations. The structural bases for the changes in dimerization are not yet fully characterized, as the monomeric form of thioredoxin has not yet been crystallized.
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3

Harish, S. "Transcriptional Regulation By Nuclear Receptor Homodimers Binding To The Direct Repeat Motif DR1 : Investigations In An in vitro Transcription System Derived From Rat Liver Nuclear Extracts." Thesis, Indian Institute of Science, 2000. http://hdl.handle.net/2005/164.

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Nuclear receptors (NRs) are important transcription factors involved in the regulation of a variety of physiological processes such as embryonic development, cell differentiation and homeostasis (for review, see Mangelsdorf et al., 1995 TenBaum and Baniahrned, 1997). In contrast to membrane bound receptors, they bind small lipophilic ligands and function in the nucleus as ligand-modulated transcription factors. The ligands for nuclear receptors include steroids (glucocorticoids, progestins, mineralocorticoids, androgens and estrogens), vitamin D3, retinoids, thyroid hormone, prostaglandins, farnesoids etc. Several other nuclear receptors are classified as orphan receptors for which no ligand has yet been identified. More than 300 nuclear receptors have now been identified and together these proteins comprise the single largest family of metazoan transcription factors, the nuclear receptor superfamily. Recently, a unified nomenclature has been evolved (nuclear receptor nomenclature committee, 1999), a summary of which is presented in Table 1.
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4

Silva, Wagner André Vieira da. "Uso da estratégia drogas gêmeas para a síntese de novos homodimeros de adutos de morita-bayllis- hilman potenciais candidatos a fármacos antiparasitários." Universidade Federal da Paraíba, 2016. http://tede.biblioteca.ufpb.br:8080/handle/tede/9022.

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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES
This work was performed in order to synthesize and bioavaliar the activity of new adducts Morita-Baylis-Hillman (AMBH) as potential drug candidates. The AMBH were synthesized from the twin drug approach (approach twin drugs) and bioavaliados against Leishmania promastigote form donovanii, a kind of visceral leishmaniasis and more severe disease, which has a drug used for the treatment accompanied by high toxicity. As Michael acceptor to be used in Morita-Baylis-Hillman (MRBH) was synthesized diacrylate ethylene glycol (50) from the esterification reaction between ethylene glycol (65) and acrylic acid (66). The first MRBH was investigated between two equivalent 2-nitrobenzaldehyde (57) and one equivalent of diacrylate 50, in acetonitrile as solvent in the presence of DABCO, yielding two products: an adduct 67 and an adduct homodimeric 42. In investigations of experimental parameters the MRBH, DMF, DABCO and room temperature proved to be the most favorable conditions for the formation of adducts homodimeric, these being obtained in yields of 35-94% and reaction times between 24 and 20 days, isolated by liquid / liquid and via flash chromatography. Homodimers and other bioavaliados AMBH results were satisfactory to excellent IC50 for homodimeric adducts (IC50 126.20 to 0,50M). All homodimeric AMBH had higher bioactivity the corresponding AMBH, showing the success of the twin drugs approach against promastigote species of leishmania donovanii, reaching the impressive result, in the case of 49 homodimer be 393.1 times more active than the corresponding AMBH 56, being 1.24 more active than the anfoterinica B, and no reported toxicity exposure in red blood cells of human blood (iS> 400 against iS = 18.73 amphotericin B). These results show that 49 homodimer is a promising molecule in the search for new drug candidates.
Este trabalho foi realizado com o objetivo de sintetizar e bioavaliar a atividade de novos Adutos de Morita-Baylis-Hillman (AMBH) como potenciais candidatos a fármacos. Os AMBH foram sintetizados a partir da abordagem drogas gêmeas (twin drugs approach) e bioavaliados contra a forma promastigota Leishmania donovanii, uma espécie da forma visceral e mais grave da doença, a qual possui o fármaco utilizado para o tratamento acompanhado de grande toxicidade. Como aceptor de Michael para ser utilizado na reação de Morita-Baylis-Hillman (RMBH), foi sintetizado o diacrilato do etileno glicol (50) a partir da reação de esterificação entre o etileno glicol (65) e o ácido acrílico (66). A primeira RMBH investigada foi entre dois equivalentes 2-nitrobenzaldeído (57) e um equivalente do diacrilato 50, em acetonitrila como solvente na presença de DABCO, obtendo-se dois produtos: um aduto 67 e um aduto homodimérico 42. Nas investigações dos parâmetros experimentais da RMBH, o DMF, o DABCO e a temperatura ambiente mostraram ser as condições mais favoráveis para a formação dos adutos homodiméricos, sendo esses obtidos com rendimentos entre 35-94% e em tempos reacionais entre 24h e 20 dias, isolados por extração líquido/líquido e via cromatográfia flash. Os homodímeros e os demais AMBH bioavaliados tiveram resultados de satisfatórios a excelentes de CI50 para os adutos homodiméricos (CI50 126,20 a 0,50M). Todos os AMBH homodiméricos tiveram bioatividade superior aos AMBH correspondentes, evidenciando o sucesso da abordagem de drogas gêmeas contra a espécie promastigota da leishmania donovanii, chegando ao impressionante resultado, no caso do homodímero 49, ser 393,1 vezes mais ativo que o AMBH correspondente 56, sendo 1.24 mais ativo que a anfoterinica B, além de não apresentar toxicidade na exposição em glóbulos vermelhos do sangue humano (IS > 400, contra IS = 18,73 da anfotericina B). Estes resultados evidenciam que homodímero 49 é uma molécula promissora na busca de novos candidatos a fármacos.
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5

Clement, Ella Chow. "Design and Syntheses of Potential Drugs Based on GABA(A) Receptor Pharmacophores." Diss., Virginia Tech, 2005. http://hdl.handle.net/10919/28271.

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Numerous previous studies of GABAAR ligands have suggested that GABAAR agonists must be zwitterionic and feature an intercharge separation similar to that of GABA (approx. 4.7-6.0 Ã ). We have demonstrated that monomeric, homodimeric and heterodimeric non-zwitterionic GABA amides are partial, full, or superagonists at the murine GABAA receptor (GABAAR). The agonism of these GABA amides is comparable to that of THIP, as shown by in vitro assay results. The assay data indicate that the agonism of GABA amides is tether length-dependent. Optimum agonism is achieved with a tether length of four methylenes in GABA amide dimers and in GABA amides bearing pendant amide or amino groups. We have further investigated the structure-activity relationship for GABA amides on the GABAAR by performing structural modifications to both the superagonist 2c and the agonist 6c. Synergism and [3H]muscimol binding experiments show that 2c binds to the same sites as GABA. Structural modification of 2c demonstrated that partial rigidification of the tether eliminated agonism and caused ligands to behave as weak competitive antagonists. We have also investigated the agonism of four ZAPA derivatives in 36Cl- uptake functional assay. Two of them are found to be as potent as GABA. In our studies of 1,4-benzodiazepines, our goal was to synthesize three different subtypes of quaternary 1,4-benzodiazepines by use of the memory of chirality (MOC) strategy. Disappointingly, most of the deprotonation/alkylations failed, due to various reasons. The failure of the reactions of (S)-alanine-derived tetrahydro-1,4-benzodiazepin-3-ones was probably due to either the unexpected side reactions or the steric hindrance of enolate alkylation. In the case of tetrahydro-1,4-benzodiazepin-2-ones, computational studies suggested that steric hindrance by both the benzo ring and N4-allyl group might retard deprotonation at C3 by bulky bases like KHMDS or LDA. Finally, (S)-serine-derived 1,4-benzodiazepin-2-ones and their elimination products (ï ¡-methylene benzodiazepines) were prepared. These proved unreactive towards deprotonation/alkylations and conjugate additions, respectively. The low reactivity of the ï ¡-methylene benzodiazepines towards nucleophiles was attributed to highly delocalized LUMOs that failed to direct nucleophiles to the ï ¢-carbons.
Ph. D.
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6

Connerney, Jeannette J. "Balance between Formation of Twist1 Homodimer and Heterodimer Regulate Suture Fusion." Fogler Library, University of Maine, 2007. http://www.library.umaine.edu/theses/pdf/ConnerneyJJ2007.pdf.

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7

Negron, Christopher. "Computational design of orthogonal antiparallel homodimeric coiled coils." Thesis, Massachusetts Institute of Technology, 2014. http://hdl.handle.net/1721.1/93805.

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Анотація:
Thesis: Ph. D., Massachusetts Institute of Technology, Computational and Systems Biology Program, 2014.
Cataloged from PDF version of thesis.
Includes bibliographical references.
Living cells integrate a vast array of protein-protein interactions (PPIs) to govern cellular functions. For instance, PPIs are critical to biosynthesis, nanostructural assembly, and in processing environmental stimuli through cell-signaling pathways. As fields such as synthetic biology and protein engineering mature they seek to mimic and expand the functions found in living systems that integrate PPIs. A critical feature to many PPIs that are integrated together to perform a complex function is orthogonality, i.e. PPIs that do not cross interact with each other. The engineering of orthogonal PPIs is thus an alluring problem. Since it not only tests our understanding of molecular specificity by having to stabilize and destabilize interactions simultaneously. The results of the design process can also have interesting applications in synthetic biology or bionanotechnology. The coiled coil, a rope-like structure made of helices, is a PPI ubiquitously found in biological systems and is an attractive fold for engineering orthogonal PPIs. Though the coiled coil is well studied, destabilization of undesired interactions still remains challenging. In this thesis I will discuss strategies for obtaining orthogonal PPIs, and describe the current sequence-to-structure relationships known about coiled coils. I will then introduce the computational multistate design framework, CLASSY, and explain how I applied it to the computational design of six orthogonal antiparallel homodimeric coiled coils. Five of these designed sequences were experimentally tested, of which only three of the sequences adopted the target antiparallel homodimer topology. All three of these sequences, as well as a previously designed antiparallel homodimer, were tested for cross reactivity in a pairwise manner. None of these sequences appeared to cross react. The sequences that failed to adopt the antiparallel topology highlight the need for improving our computational design framework. In the final chapter I will discuss strategies to improve our models, and applications for orthogonal antiparallel coiled coils.
by Christopher Negron.
Ph. D.
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8

Shin, Jong M. "Role of C121A in mGluR2 homodimeric expression and function." VCU Scholars Compass, 2018. https://scholarscompass.vcu.edu/etd/5576.

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The group II metabotropic glutamate receptors are known for their involvement in various psychiatric disorders. The mGluR2 in particular is linked with etiology of schizophrenia especially in the context of crosstalk with 5-HT2A. Thus, the mGluR2 has attracted attentions for its potential therapeutic applications. Despite numerous physiological evidences on the actions of mGluR2, its mechanism is still unclear to this day. It is partially due to the lack of understanding in characteristics of mGluR2 homodimer which is its functionally active form. Therefore, the characterization of dimeric interaction serves as a foundation to advanced understanding of the role of mGluR2. On that note, the role of the conserved cysteine residue (C121) in the ligand binding domain of mGluR2 has been evaluated in this study as they are known to play a critical part in homodimer formation. Collectively, C121 has been shown to affect the dimerization, subcellular localization, and pharmacokinetics of mGluR2. Lastly, the effect of mGluR2 on mouse behavior was examined in a partial effort to elucidate its role in crosstalk with 5-HT2A.
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9

Mcgeagh, John David. "Conformation and cooperativity in homodimeric enzymes investigated by molecular dynamics simulations." Thesis, University of Bristol, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.549446.

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10

Lin, Yi-Jan. "Solution structure of the 30 kDa homodimeric sud protein from Wolinella succinogenes." [S.l.] : [s.n.], 2003. http://deposit.ddb.de/cgi-bin/dokserv?idn=968620817.

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Книги з теми "Homodimers"

1

Ohsawa, Kosuke. Total Synthesis of Thielocin B1 as a Protein-Protein Interaction Inhibitor of PAC3 Homodimer. Tokyo: Springer Japan, 2015. http://dx.doi.org/10.1007/978-4-431-55447-9.

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2

Ohsawa, Kosuke. Total Synthesis of Thielocin B1 as a Protein-Protein Interaction Inhibitor of PAC3 Homodimer. Springer, 2015.

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3

Ohsawa, Kosuke. Total Synthesis of Thielocin B1 as a Protein-Protein Interaction Inhibitor of PAC3 Homodimer. Springer, 2015.

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4

Ohsawa, Kosuke. Total Synthesis of Thielocin B1 as a Protein-Protein Interaction Inhibitor of PAC3 Homodimer. Springer, 2016.

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5

Ohsawa, Kosuke. Total Synthesis of Thielocin B1 As a Protein-Protein Interaction Inhibitor of PAC3 Homodimer. Springer Japan, 2015.

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Частини книг з теми "Homodimers"

1

Chan, Bun, Janet E. Del Bene, and Leo Radom. "Proton-bound homodimers involving second-row atoms." In Highlights in Theoretical Chemistry, 15–22. Berlin, Heidelberg: Springer Berlin Heidelberg, 2012. http://dx.doi.org/10.1007/978-3-642-31750-7_3.

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2

Graddis, Tom, and Irwin Chaiken. "Designing homodimers and heterodimers with sequence simplified leucine zipper models." In Peptides, 360–61. Dordrecht: Springer Netherlands, 1992. http://dx.doi.org/10.1007/978-94-011-2264-1_132.

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3

Yang, Guoqian, Xiaorui Liu, and Li Lin. "Detection of UVR8 Homodimers and Monomers by Immunoblotting Analysis in." In Methods in Molecular Biology, 83–93. New York, NY: Springer US, 2021. http://dx.doi.org/10.1007/978-1-0716-1370-2_9.

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4

Melnyk, Roman A., Anthony W. Partridge, and Charles M. Deber. "Transmembrane Segment Peptides of the Ff Phage Major Coat Protein Form Parallel Homodimers." In Peptides: The Wave of the Future, 824–25. Dordrecht: Springer Netherlands, 2001. http://dx.doi.org/10.1007/978-94-010-0464-0_385.

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5

Kangueane, Pandjassarame. "Homodimer Folding and Binding." In Bioinformation Discovery, 107–16. Cham: Springer International Publishing, 2018. http://dx.doi.org/10.1007/978-3-319-95327-4_5.

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6

Kangueane, Pandjassarame. "Homodimer Folding and Binding." In Bioinformation Discovery, 87–96. New York, NY: Springer New York, 2009. http://dx.doi.org/10.1007/978-1-4419-0519-2_5.

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7

Kangueane, Pandjassarame, and Christina Nilofer. "Homodimer Protein Folding and Binding." In Protein-Protein and Domain-Domain Interactions, 125–32. Singapore: Springer Singapore, 2018. http://dx.doi.org/10.1007/978-981-10-7347-2_10.

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8

Hager-Braun, Christine, Rainer Zimmermann, and Günter Hauska. "The Homodimeric Reaction Center of Chlorobium." In The Phototrophic Prokaryotes, 169–81. Boston, MA: Springer US, 1999. http://dx.doi.org/10.1007/978-1-4615-4827-0_20.

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9

Görisch, H., T. Keitel, A. Diehl, T. Knaute, Z. Dauter, and W. Höhne. "Structural properties of homodimeric quinoprotein ethanol deyhdrogenase from." In Biochemistry and Molecular Biology of Vitamin B6 and PQQ-dependent Proteins, 55–60. Basel: Birkhäuser Basel, 2000. http://dx.doi.org/10.1007/978-3-0348-8397-9_9.

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10

Petkov, Peicho, Elena Lilkova, Nevena Ilieva, Genoveva Nacheva, Ivan Ivanov, and Leandar Litov. "Computational Modelling of the Full Length hIFN- $$\gamma $$ γ Homodimer." In Large-Scale Scientific Computing, 544–51. Cham: Springer International Publishing, 2018. http://dx.doi.org/10.1007/978-3-319-73441-5_60.

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Тези доповідей конференцій з теми "Homodimers"

1

Marshall, Mark, Wolfgang Jäger, Yunjie Xu, Nathan Seifert, and Helen Leung. "EFFECTS OF CHIRALITY IN HOMODIMERS OF 3,3,3-TRIFLUORO-1,2-EPOXYPROPANE." In 73rd International Symposium on Molecular Spectroscopy. Urbana, Illinois: University of Illinois at Urbana-Champaign, 2018. http://dx.doi.org/10.15278/isms.2018.tc04.

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2

Juanes, Marcos, Jens-Uwe Grabow, Daniel Obenchain, Luca Evangelisti, Josﾎ Rubio, Ruth Pinacho, Alberto Lesarri, and Rizalina Saragi. "HYDROGEN BONDING IN THE MONOHYDRATES AND HOMODIMERS OF CYCLOHEXYLAMINE AND CYCLOHEXANETHIOL." In 74th International Symposium on Molecular Spectroscopy. Urbana, Illinois: University of Illinois at Urbana-Champaign, 2019. http://dx.doi.org/10.15278/isms.2019.rh04.

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3

Wu, Jieyun, Bo Wu, Wen Wang, Kin Seng Chiang, Alex K.-Y. Jen, and Jingdong Luo. "Ultra-efficient and stable EO dendrimers containing supramolecular homodimers of dipolar semifluorinated aromatics." In CLEO: Applications and Technology. Washington, D.C.: OSA, 2018. http://dx.doi.org/10.1364/cleo_at.2018.jtu2a.147.

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4

del Molino del Barrio, Irene, Simi Ali, John Kirby, and Annette Meeson. "Abstract 1453: CXCR4 and CXCR7 homodimers and heterodimers play differential roles in breast cancer." In Proceedings: AACR 107th Annual Meeting 2016; April 16-20, 2016; New Orleans, LA. American Association for Cancer Research, 2016. http://dx.doi.org/10.1158/1538-7445.am2016-1453.

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5

Marshall, Mark, and Helen Leung. "MICROWAVE SPECTRA AND MOLECULAR STRUCTURES OF THE GAS-PHASE HOMOCHIRAL HOMODIMERS OF 3,3-DIFLUORO-1,2-EPOXYPROPANE AND 3-FLUORO-1,2-EPOXYPROPANE." In 2020 International Symposium on Molecular Spectroscopy. Urbana, Illinois: University of Illinois at Urbana-Champaign, 2020. http://dx.doi.org/10.15278/isms.2020.wk02.

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6

Marshall, Mark, and Helen Leung. "MICROWAVE SPECTRA AND MOLECULAR STRUCTURES OF THE GAS-PHASE HOMOCHIRAL HOMODIMERS OF 3,3-DIFLUORO-1,2-EPOXYPROPANE AND 3-FLUORO-1,2-EPOXYPROPANE." In 2021 International Symposium on Molecular Spectroscopy. Urbana, Illinois: University of Illinois at Urbana-Champaign, 2021. http://dx.doi.org/10.15278/isms.2021.rk01.

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7

Saragi, Rizalina, Martin Jaraiz, Lourdes Enriquez, Alberto Lesarri, and Marcos Juanes. "OBSERVATION OF 2-NAPHTHALENETHIOL HOMODIMER USING ROTATIONAL SPECTROSCOPY." In 2021 International Symposium on Molecular Spectroscopy. Urbana, Illinois: University of Illinois at Urbana-Champaign, 2021. http://dx.doi.org/10.15278/isms.2021.wd07.

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8

Niiya, K., P. Kostel, T. S. Zimmerman, and Z. M. Ruggeri. "CHARACTERIZATION OF A 40 kDa FRAGMENT OF VON WILLEBRAND FACTOR THAT CONTAINS THE GLYCOPROTEIN IIb/IIIa-BINDING DOMAIN." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1642874.

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We have isolated a 40 kDa fragment of von Willebrand factor (vWF) that contains the glycoprotein (GP) Ilb/IIIa-binding domain. The Staphylococcus aureus V8 protease-generated fragment II was digested with trypsin (1:50 enzyme:substrate ratio on a weight-to-weight basis). After addition of a 100fold molar excess of (p-amidinophenyl)methanesulfonyl fluoride in order to inhibit any residual trypsin activity, the whole digest was subjected to ion-exchange and size-exclusion high pressure liquid chromatography. Two major fragments were separated. Analysis by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate (SDS) demonstrated that one of the two purified polypeptides had an apparent molecular weight of 40 kDa under both reducing and nonreducing conditions, suggesting that it was a single chain polypeptide. The other fragment had an apparent molecular weight of 22 kDa after reduction and 44 kDa unreduced, suggesting that it was a homodimer. Amino terminal sequence analysis of both fragments was performed by classical Edman degradation following electroelution from reduced SDS-polyacrylamide gels. The amino terminus of the 40 kDa fragment corresponded to residue Glu (1366) (as did the fragment II from which it was derived), while the amino terminus of the 22 kDa fragment corresponded to residue Val (1927) of the constituent 2050 residue subunit. The effect of both fragments on vWF binding to the platelet membrane GP IIb/IIIa complex was evaluated by measuring the residual binding of 125I-labeled vWF to thrombin-stimulated platelets in the presence of varying amounts of the unreduced fragments. The 40 kDa polypeptide inhibited 64 percent of vWF binding when tested at a concentration of 20 μK, whereas the 22kDa dimer was without effect. This study establishes that the GP IIb/IIIa-binding domain of vWF resides in a discrete, single-chain 40 kDa fragment derived from the 220 kDa, homodimeric fragment II generated by V8 protease. Moreover, we found evidence for the existence of inter-chain disulfide bonds within 22 kDa from the carboxyl terminus of the constituent subunit.
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9

Du, Mengfang. "Bursicon homodimer actions in the immune response ofHelicoverpa armigera." In 2016 International Congress of Entomology. Entomological Society of America, 2016. http://dx.doi.org/10.1603/ice.2016.93604.

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10

Sonzini, Silvia, Frank Biedermann, and Oren A. Scherman. "Synthesis of Photoswitchable Homodimeric Polypeptides: Towards Biological Applications." In The Twenty-Third American and the Sixth International Peptide Symposium. Prompt Scientific Publishing, 2013. http://dx.doi.org/10.17952/23aps.2013.244.

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Звіти організацій з теми "Homodimers"

1

Golbeck, John. The Type 1 Homodimeric Reaction Center in Heliobacterium modesticaldum. Office of Scientific and Technical Information (OSTI), January 2018. http://dx.doi.org/10.2172/1416952.

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2

Vitetta, Ellen S. The Generation and Preclinical Evaluation of Homodimeric Anti-Her-2 Antibodies. Fort Belvoir, VA: Defense Technical Information Center, April 2001. http://dx.doi.org/10.21236/ada395803.

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3

Bazer, Fuller W., Arieh Gertler, and Elisha Gootwine. Role of Placental Lactogen in Sheep. United States Department of Agriculture, January 2001. http://dx.doi.org/10.32747/2001.7574339.bard.

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Central problems in sheep and dairy cattle production are reproductive failure due to embryonic/fetal mortality and low birth weights, especially in prolific breeds, and reduced milk yields which adversely affect neonatal survival and economy of production. The sheep placenta expresses lactogenic (ovine placental lactogen, oPL) and somatogenic (ovine placental growth hormone, oGH) hormones. Our research has focused on the biological roles of oPL and oGH in function of the uterine endometrium during gestation and the mammary gland during pregnancy and lactation. Major conclusions were that: ( 1 ) immunization of prepubertal ewes against oPL resulted in increased birth weights of their lambs and their milk production during lactation; (2) neither oPL nor oGH had an antiluteolytic effect on uterine endometrium to affect lifespan of the corpus luteum; (3) only sequential exposure of the progesterone stimulated uterus to oIFNt and oPL or oGH increased endometrial gland proliferation and secretory protein gene expression; (4) oPL signals through a homodimer of ovine prolactin receptor (PRL-R) and heterodimer of oPRL-R and growth hormone receptor (GH-R); (5) exogenous recombinant oPL and oGH stimulated mammogenesis and milk yield during lactation; and (6) mutation of oPL and oGH was used to define specific biological effects and a rational basis for design of a specific receptor agonists or antagonists. This project was very productive in elucidating basic biological effects of oPL and oGH on intracellular signal transduction pathways, uterine development and secretory function, as well as mammogenesis and lactogenesis. We determined that immunization of prepubertal ewes against roPL increased birth weights of their lambs, especially those born as twins and triplets, as well as enhanced lactational performance. These studies significantly extended our knowledge of uterine and fetal-placental physiology and provided a foundation for new strategies to enhance reproductive and lactation efficiency. Based on these results, the major achievements were: 1) creation of a practical and cost effective management tool for producers to increase reproductive performance, neonatal survival, and milk yield of ewes in commercial flocks; and 2) define, for the first time, biological effects of oPL on endometrial functions and gene expression by uterine gland epithelium.
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4

Sessa, Guido, та Gregory Martin. MAP kinase cascades activated by SlMAPKKKε and their involvement in tomato resistance to bacterial pathogens. United States Department of Agriculture, січень 2012. http://dx.doi.org/10.32747/2012.7699834.bard.

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The research problem: Pseudomonas syringae pv. tomato (Pst) and Xanthomonas campestrispv. vesicatoria (Xcv) are the causal agents of tomato bacterial speck and spot diseases, respectively. These pathogens colonize the aerial parts of the plant and cause economically important losses to tomato yield worldwide. Control of speck and spot diseases by cultural practices or chemicals is not effective and genetic sources of resistance are very limited. In previous research supported by BARD, by gene expression profiling we identified signaling components involved in resistance to Xcvstrains. Follow up experiments revealed that a tomato gene encoding a MAP kinase kinase kinase (MAPKKKe) is required for resistance to Xcvand Pststrains. Goals: Central goal of this research was to investigate the molecular mechanisms by which MAPKKKεand associated MAP kinase cascades regulate host resistance. Specific objectives were to: 1. Determine whether MAPKKKεplays a broad role in defense signaling in plants; 2. Identify components of MAP kinase cascades acting downstream of MAPKKKε; 3. Determine the role of phosphorylation-related events in the function of MAPKKKε; 4. Isolate proteins directly activated by MAPKKKε-associatedMAPK modules. Our main achievements during this research program are in the following major areas: 1. Characterization of MAPKKKεas a positive regulator of cell death and dissection of downstream MAP kinase cascades (Melech-Bonfil et al., 2010; Melech-Bonfil and Sessa, 2011). The MAPKKKεgene was found to be required for tomato resistance to Xcvand Pstbacterial strains and for hypersensitive response cell death triggered by different R gene/effector gene pairs. In addition, overexpression analysis demonstrated that MAPKKKεis a positive regulator of cell death, whose activity depends on an intact kinase catalytic domain. Epistatic experiments delineated a signaling cascade downstream of MAPKKKεand identified SIPKK as a negative regulator of MAPKKKε-mediated cell death. Finally, genes encoding MAP kinase components downstream of MAPKKKεwere shown to contribute to tomato resistance to Xcv. 2. Identification of tomato proteins that interact with MAPKKKεand play a role in plant immunity (Oh et al., 2011). We identified proteins that interact with MAPKKKε. Among them, the 14-3-3 protein TFT7 was required for cell death mediated by several R proteins. In addition, TFT7 interacted with the MAPKK SlMKK2 and formed homodimersin vivo. Thus, TFT7 is proposed to recruit SlMKK2 and MAPKKK client proteins for efficient signal transfer. 3. Development of a chemical genetic approach to identify substrates of MAPKKKε-activated MAP kinase cascades (Salomon et al., 2009, 2011). This approach is based on engineering the kinase of interest to accept unnatural ATP analogs. For its implementation to identify substrates of MAPKKKε-activated MAP kinase modules, we sensitized the tomato MAP kinase SlMPK3 to ATP analogs and verified its ability to use them as phosphodonors. By using the sensitized SlMPK3 and radiolabeled N6(benzyl)ATP it should be possible to tag direct substrates of this kinase. 4. Development of methods to study immunity triggered by pathogen-associated molecular patterns (PAMPs) in tomato and N. benthamiana plants (Kim et al., 2009; Nguyen et al. 2010). We developed protocols for measuring various PTI-associatedphenotypes, including bacterial populations after pretreatment of leaves with PAMPs, induction of reporter genes, callose deposition at the cell wall, activation of MAP kinases, and a luciferase-based reporter system for use in protoplasts. Scientific and agricultural significance: Our research activities discovered and characterized a signal transduction pathway mediating plant immunity to bacterial pathogens. Increased understanding of molecular mechanisms of immunity will allow them to be manipulated by both molecular breeding and genetic engineering to produce plants with enhanced natural defense against disease. In addition, we successfully developed new biochemical and molecular methods that can be implemented in the study of plant immunity and other aspects of plant biology.
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