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Статті в журналах з теми "Hexameric proteins":
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Skálová, Tereza, Jan Bláha, Karl Harlos, Jarmila Dušková, Tomáš Koval', Jan Stránský, Jindřich Hašek, Ondřej Vaněk, and Jan Dohnálek. "Four crystal structures of human LLT1, a ligand of human NKR-P1, in varied glycosylation and oligomerization states." Acta Crystallographica Section D Biological Crystallography 71, no. 3 (February 26, 2015): 578–91. http://dx.doi.org/10.1107/s1399004714027928.
Анотація:
Human LLT1 is a C-type lectin-like ligand of NKR-P1 (CD161, geneKLRB1), a C-type lectin-like receptor of natural killer cells. Using X-ray diffraction, the first experimental structures of human LLT1 were determined. Four structures of LLT1 under various conditions were determined: monomeric, dimeric deglycosylated after the firstN-acetylglucosamine unit in two forms and hexameric with homogeneous GlcNAc2Man5glycosylation. The dimeric form follows the classical dimerization mode of human CD69. The monomeric form keeps the same fold with the exception of the position of an outer part of the long loop region. The hexamer of glycosylated LLT1 consists of three classical dimers. The hexameric packing may indicate a possible mode of interaction of C-type lectin-like proteins in the glycosylated form.
2
Jomaa, Ahmad, Jack Iwanczyk, Julie Tran, and Joaquin Ortega. "Characterization of the Autocleavage Process of the Escherichia coli HtrA Protein: Implications for its Physiological Role." Journal of Bacteriology 191, no. 6 (December 19, 2008): 1924–32. http://dx.doi.org/10.1128/jb.01187-08.
Анотація:
ABSTRACT The Escherichia coli HtrA protein is a periplasmic protease/chaperone that is upregulated under stress conditions. The protease and chaperone activities of HtrA eliminate or refold damaged and unfolded proteins in the bacterial periplasm that are generated upon stress conditions. In the absence of substrates, HtrA oligomerizes into a hexameric cage, but binding of misfolded proteins transforms the hexamers into bigger 12-mer and 24-mer cages that encapsulate the substrates for degradation or refolding. HtrA also undergoes partial degradation as a consequence of self-cleavage of the mature protein, producing short-HtrA protein (s-HtrA). The aim of this study was to examine the physiological role of this self-cleavage process. We found that the only requirement for self-cleavage of HtrA into s-HtrA in vitro was the hydrolysis of protein substrates. In fact, peptides resulting from the hydrolysis of the protein substrates were sufficient to induce autocleavage. However, the continuous presence of full-length substrate delayed the process. In addition, we observed that the hexameric cage structure is required for autocleavage and that s-HtrA accumulates only late in the degradation reaction. These results suggest that self-cleavage occurs when HtrA reassembles back into the resting hexameric structure and peptides resulting from substrate hydrolysis are allosterically stimulating the HtrA proteolytic activity. Our data support a model in which the physiological role of the self-cleavage process is to eliminate the excess of HtrA once the stress conditions cease.
3
Myasoedova, Ksenia N., and Natalia N. Magretova. "Cross-Linking Study of Cytochrome P450 1A2 in Proteoliposomes." Bioscience Reports 21, no. 1 (February 1, 2001): 63–72. http://dx.doi.org/10.1023/a:1010486118448.
Анотація:
Proteoliposomes, containing cytochrome P450 1A2, were obtained by the cholate-dialysis technique. The effect of bifunctional cross-linking reagents on the purified hexameric cytochrome P450 1A2 in an aqueous medium and on the proteoliposomal P450 1A2 have been compared. Electrophoretic analysis of the modified proteins demonstrated the same oligomeric (hexameric) organization of the hemoprotein in each case.
4
Chaudhury, Paushali, Chris van der Does, and Sonja-Verena Albers. "Characterization of the ATPase FlaI of the motor complex of the Pyrococcus furiosus archaellum and its interactions between the ATP-binding protein FlaH." PeerJ 6 (June 18, 2018): e4984. http://dx.doi.org/10.7717/peerj.4984.
Анотація:
The archaellum, the rotating motility structure of archaea, is best studied in the crenarchaeon Sulfolobus acidocaldarius. To better understand how assembly and rotation of this structure is driven, two ATP-binding proteins, FlaI and FlaH of the motor complex of the archaellum of the euryarchaeon Pyrococcus furiosus, were overexpressed, purified and studied. Contrary to the FlaI ATPase of S. acidocaldarius, which only forms a hexamer after binding of nucleotides, FlaI of P. furiosus formed a hexamer in a nucleotide independent manner. In this hexamer only 2 of the ATP binding sites were available for binding of the fluorescent ATP-analog MANT-ATP, suggesting a twofold symmetry in the hexamer. P. furiosus FlaI showed a 250-fold higher ATPase activity than S. acidocaldarius FlaI. Interaction studies between the isolated N- and C-terminal domains of FlaI showed interactions between the N- and C-terminal domains and strong interactions between the N-terminal domains not previously observed for ATPases involved in archaellum assembly. These interactions played a role in oligomerization and activity, suggesting a conformational state of the hexamer not observed before. Further interaction studies show that the C-terminal domain of PfFlaI interacts with the nucleotide binding protein FlaH. This interaction stimulates the ATPase activity of FlaI optimally at a 1:1 stoichiometry, suggesting that hexameric PfFlaI interacts with hexameric PfFlaH. These data help to further understand the complex interactions that are required to energize the archaellar motor.
5
Jomaa, Ahmad, Daniela Damjanovic, Vivian Leong, Rodolfo Ghirlando, Jack Iwanczyk, and Joaquin Ortega. "The Inner Cavity of Escherichia coli DegP Protein Is Not Essentialfor Molecular Chaperone and Proteolytic Activity." Journal of Bacteriology 189, no. 3 (November 22, 2006): 706–16. http://dx.doi.org/10.1128/jb.01334-06.
Анотація:
ABSTRACT The Escherichia coli DegP protein is an essential periplasmic protein for bacterial survival at high temperatures. DegP has the unusual property of working as a chaperone below 28°C, but efficiently degrading unfolded proteins above 28°C. Monomeric DegP contains a protease domain and two PDZ domains. It oligomerizes into a hexameric cage through the staggered association of trimers. The active sites are located in a central cavity that is only accessible laterally, and the 12 PDZ domains act as mobile sidewalls that mediate opening and closing of the gates. As access to the active sites is restricted, DegP is an example of a self-compartmentalized protease. To determine the essential elements of DegP that maintain the integrity of the hexameric cage, we constructed several deletion mutants of DegP that formed trimers rather than hexamers. We found that residues 39 to 78 within the LA loops, as well as the PDZ2 domains are essential for the integrity of the DegP hexamer. In addition, we asked whether an enclosed cavity or cage of specific dimensions is required for the protease and chaperone activities in DegP. Both activities were maintained in the trimeric DegP mutants without an enclosed cavity and in deletion DegP mutants with significantly reduced dimensions of the cage. We conclude that the functional unit for the protease and chaperone activities of DegP is a trimer and that neither a cavity of specific dimensions nor the presence of an enclosed cavity appears to be essential for the protease and chaperone activities of DegP.
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Miller, Justin M., and Eric J. Enemark. "Archaeal MCM Proteins as an Analog for the Eukaryotic Mcm2–7 Helicase to Reveal Essential Features of Structure and Function." Archaea 2015 (2015): 1–14. http://dx.doi.org/10.1155/2015/305497.
Анотація:
In eukaryotes, the replicative helicase is the large multisubunit CMG complex consisting of the Mcm2–7 hexameric ring, Cdc45, and the tetrameric GINS complex. The Mcm2–7 ring assembles from six different, related proteins and forms the core of this complex. In archaea, a homologous MCM hexameric ring functions as the replicative helicase at the replication fork. Archaeal MCM proteins form thermostable homohexamers, facilitating their use as models of the eukaryotic Mcm2–7 helicase. Here we review archaeal MCM helicase structure and function and how the archaeal findings relate to the eukaryotic Mcm2–7 ring.
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Sellin, Mikael E., Sonja Stenmark, and Martin Gullberg. "Mammalian SEPT9 isoforms direct microtubule-dependent arrangements of septin core heteromers." Molecular Biology of the Cell 23, no. 21 (November 2012): 4242–55. http://dx.doi.org/10.1091/mbc.e12-06-0486.
Анотація:
Septin-family proteins assemble into rod-shaped heteromeric complexes that form higher-order arrangements at the cell cortex, where they serve apparently conserved functions as diffusion barriers and molecular scaffolds. There are 13 confirmed septin paralogues in mammals, which may be ubiquitous or tissue specific. Septin hetero-oligomerization appears homology subgroup directed, which in turn determines the subunit arrangement of six- to eight-subunit core heteromers. Here we address functional properties of human SEPT9, which, due to variable mRNA splicing, exists as multiple isoforms that differ between tissues. Myeloid K562 cells express three SEPT9 isoforms, all of which have an equal propensity to hetero-oligomerize with SEPT7-containing hexamers to generate octameric heteromers. However, due to limiting amounts of SEPT9, K562 cells contain both hexameric and octameric heteromers. To generate cell lines with controllable hexamer-to-octamer ratios and that express single SEPT9 isoforms, we developed a gene product replacement strategy. By this means we identified SEPT9 isoform–specific properties that either facilitate septin heteromer polymerization along microtubules or modulate the size range of submembranous septin disks—a prevalent septin structure in nonadhered cells. Our findings show that the SEPT9 expression level directs the hexamer-to-octamer ratio, and that the isoform composition and expression level together determine higher-order arrangements of septins.
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Zhao, Li, Shuji Kanamaru, Chatree'chalerm Chaidirek, and Fumio Arisaka. "P15 and P3, the Tail Completion Proteins of Bacteriophage T4, Both Form Hexameric Rings." Journal of Bacteriology 185, no. 5 (March 1, 2003): 1693–700. http://dx.doi.org/10.1128/jb.185.5.1693-1700.2003.
Анотація:
ABSTRACT Two proteins, gp15 and gp3 (gp for gene product), are required to complete the assembly of the T4 tail. gp15 forms the connector which enables the tail to bind to the head, whereas gp3 is involved in terminating the elongation of the tail tube. In this work, genes 15 and 3 were cloned and overexpressed, and the purified gene products were studied by analytical ultracentrifugation, electron microscopy, and circular dichroism. Determination of oligomerization state by sedimentation equilibrium revealed that both gp15 and gp3 are hexamers of the respective polypeptide chains. Electron microscopy of the negatively stained P15 and P3 (P denotes the oligomeric state of the gene product) revealed that both proteins form hexameric rings, the diameter of which is close to that of the tail tube. The differential roles between gp15 and gp3 upon completion of the tail are discussed.
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Ochoa, Jessica M., Oscar Mijares, Andrea A. Acosta, Xavier Escoto, Nancy Leon-Rivera, Joanna D. Marshall, Michael R. Sawaya, and Todd O. Yeates. "Structural characterization of hexameric shell proteins from two types of choline-utilization bacterial microcompartments." Acta Crystallographica Section F Structural Biology Communications 77, no. 9 (August 24, 2021): 275–85. http://dx.doi.org/10.1107/s2053230x21007470.
Анотація:
Bacterial microcompartments are large supramolecular structures comprising an outer proteinaceous shell that encapsulates various enzymes in order to optimize metabolic processes. The outer shells of bacterial microcompartments are made of several thousand protein subunits, generally forming hexameric building blocks based on the canonical bacterial microcompartment (BMC) domain. Among the diverse metabolic types of bacterial microcompartments, the structures of those that use glycyl radical enzymes to metabolize choline have not been adequately characterized. Here, six structures of hexameric shell proteins from type I and type II choline-utilization microcompartments are reported. Sequence and structure analysis reveals electrostatic surface properties that are shared between the four types of shell proteins described here.
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Heinemann, Udo, Yvette Roske, Anup Arumughan, and Erich Wanker. "Remodeling of the AAA+ ATPase p97 by the UBX Adaptor Protein ASPL." Acta Crystallographica Section A Foundations and Advances 70, a1 (August 5, 2014): C430. http://dx.doi.org/10.1107/s2053273314095692.
Анотація:
The hexameric mammalian AAA+ ATPase p97, also known as VCP (valosin-containing protein; CDC48 in yeast), is a very abundant cytosolic protein and serves a wide variety of cellular functions. p97 is a central component in endoplasmic reticulum-associated degradation (ERAD) of proteins where it delivers ubiquitinated ERAD substrates to the proteasome. In addition, cellular roles of p97 in organelle membrane fusion, mitosis, DNA repair and suppression of apoptosis have been described. These different functions are linked to the binding of adaptor proteins to p97. Many of these adaptors contain ubiquitin regulatory X (UBX) domains. ASPL (alveolar soft part sarcoma locus, also known as TUG) was recenty identified as a p97 adaptor protein. As shown by crystal structure analysis, ASPL uses a substantially extended UBX domain for binding to the N domain of p97 where a lariat-like, mostly α-helical extension wraps around one subunit of p97. By this binding ASPL triggers the dissociation of functional p97 hexamers and the formation of p97:ASPL heterotetramers with 2:2 stoichiometry, leading to inactivation of the AAA+ ATPase. The p97-ASPL interaction in the heterotetramer is very tight, but p97 hexamer dissociation and heterotetramer formation may be suppressed by single-site mutations at p97-ASPL interfaces. p97 hexamer dissociation and p97-ASPL heterotetramer formation are linked to reduced ATPase activity of p97, cellular accumulation of ERAD substrates and apoptosis induction. To the best of our knowledge, this is the first time that the structural basis for adaptor protein-induced inactivation by hexamer dissociation of p97 and, indeed, any AAA+ ATPase has been demonstrated. This observation has far reaching implications for AAA+ ATPase-regulated processes.
Дисертації з теми "Hexameric proteins":
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Barthe, Lucie. "Les microcompartiments bactériens : étude de l'assemblage des protéines hexamériques des coques et développement d'outils pour les nanotechnologies." Electronic Thesis or Diss., Université de Toulouse (2023-....), 2024. http://www.theses.fr/2024TLSEI002.
Анотація:
Les microcompartiments bactériens (BMC) sont des structures protéiques naturellement présentes chez certaines bactéries dans lesquelles ils agissent comme des bioréacteurs et métabolisent des substrats spécifiques. Selon le type de BMC, le set d’enzymes encapsulé au sein du BMC peut fixer le CO2 atmosphérique ou cataboliser l’éthanolamine, le 1,2-propanediol ou la choline. La coque polyédrique des BMCs est composée de 3 sous-unités différentes dont les BMC-H, un protomère s’oligomérisant en hexamère, sous-unité principale de la coque des BMCs. Des études génomiques ont estimé une moyenne de 3,5 homologues BMC-H par opéron BMC, avec certains organismes tel que Clostridium saccharolyticum WM1 codant jusqu’à 15 BMC-H, répartis dans 3 opérons BMC différents.Bien qu’il fut longtemps considéré que seuls des homo-hexamères existaient, il fut démontré récemment que des hétéro-hexamères pouvaient également se former entre homologues BMC-H, dans 2 bactéries exprimant le β-carboxysome. En effet, les homologues BMC-H partagent généralement une forte identité de séquence, notamment sur leur interfaces intra-hexamère. Outre ouvrir à la possibilité que des hétéro-hexamères se forment dans des organismes dotés d’un autre type de BMC, ces études récentes ont soulevé la question de potentielles cross-interactions entre BMC-H venant de différents types de BMC, au sein d’un même organisme.Un objectif de ma thèse fut d’examiner la formation d’hétéro-hexamères dans la nature. Pour cela, la tripartite GFP a été adaptée à l’étude des interactions protéines-protéines entre BMC-H et appliquée au cas des BMC-H de Klebsiella pneumoniae 342. Cet organisme est en effet doté de 3 loci codant 3 BMCs de différents types, loci qui comptabilisent un total de 11 homologues BMC-H. Ainsi, en plus de nous permettre de déterminer si des hétéro-hexamères se forment en dehors des BMC-H compris dans le β-carboxysome, leur étude pourrait apporter de premiers éléments de réponse sur la possibilité de cross-interactions entre BMC-H provenant de différents types de BMC.Une nouvelle méthode pour améliorer l’efficacité catalytique d’une voie (autre que par l’ingénierie enzymatique) suscite de plus en plus d’intérêt de nos jours : l’organisation spatiale des enzymes. L’idée est qu’en plaçant à proximité ou de manière arrangée les enzymes d’une voie métabolique, il serait possible d’augmenter l’efficacité de la voie.La majorité des hexamères formés par les BMC-H ont la propriété intrinsèque de s'auto-assembler et de former des macrostructures (nanotubes, Swiss-rolls, feuillets 2D) lorsqu'ils sont exprimés seuls dans E. coli. Cette particularité a déjà été exploitée dans de multiples études pour créer un échafaudage protéique pour l’immobilisation d’enzymes. Dans ces preuves de concept, un seul BMC-H a été utilisé pour construire l'échafaudage, ce qui permettait uniquement d'immobiliser les enzymes de manière aléatoire.Nous proposons ici d'aller plus loin dans l'idée d'organisation spatiale et visons à élaborer une plateforme protéique à partir d'un hétéro-hexamère. Cet hétéro-hexamère serait composé de 2 à 6 BMC-H différents, chaque BMC-H constituant un point d'ancrage pour un futur domaine enzymatique. Avec une telle plateforme, l’organisation spatiale des enzymes serait contrôlée plus finement, ce qui améliorerait encore l’efficacité de la catalyse d’une voie métabolique.Pour atteindre cet objectif, des BMC-H ont été designés de novo par 2 équipes collaboratrices de design computationnel. Je les ai étudiés et ai recherché des couples BMC-H qui présenteraient des interfaces intra-hexamères orthogonales. En effet, pour pouvoir contrôler précisément l'organisation sur la plateforme, cela nécessiterait d'assurer un ordre spécifique des BMC-H au sein de l'hétéro-hexamère et de contrôler étroitement quel BMC-H est adjacent à quel autre et d'empêcher toute autre associationBacterial microcompartments (BMC) are protein structures, naturally found in some bacteria in which they act as bioreactor and process specific substrates. For instance, depending on the BMC type, the enzymatic set they encapsulate can fixate atmospheric CO2 or catabolize the ethanolamine, 1,2-propanediol or the choline. The BMC shell is polyhedral and is composed of 3 different subunits, including the BMC-H, a protomer associating as an hexamer which are the main and the most diverse shell subunits, in terms of number of homologs within a single BMC operon. Indeed, genomic surveys indicate an average of 3,5 BMC-H homologs per operon, with some organisms like Clostridium saccharolyticum WM1 coding for up to 15 BMC-H split between 3 BMC types.Although it has long been thought that only homo-hexamers existed, it was recently evidenced that hetero-hexamer formation occurred between BMC-H homologs in 2 different β-carboxysome-expressing bacteria. Indeed, numerous BMC-H homologs share a high sequence identity, notably at the intra-hexamer interfaces. Besides paving the way for possible hetero-hexamer formation beyond the β-carboxysome, inside organisms equipped with one BMC type, these recent studies raise the question of possible cross-interactions between BMC-H coming from multiple BMC types.One objective during my PhD thesis was to examine the occurrence of hetero-hexamers in nature. To this end, the tripartite GFP was adapted to study protein-protein interactions among BMC-H and implemented on the case study of Klebsiella pneumonia 342 BMC-H. Of note, this organism is very interesting because it has in its genome 3 BMC loci, comprising a total of 11 BMC-H homologs. Then, besides allowing to determine whether hetero-hexamers do form aside from the β-CBX, in 3 other BMC types, their study would also bring some answer elements to the question of the cross-interactions between BMC-H arising from different BMC types.A novel method to enhance a pathway catalytic efficiency (other than by classical enzymatic engineering) is gaining more and more interests nowadays: enzyme spatial organization. The idea is that, by putting in close proximity or in an arranged fashion the enzymes from a metabolic pathway, one could increase the efficiency of the pathway, through substrate channelling between the different enzymes, for instance, or enzyme clusterisation.The majority of hexamers formed by the BMC-H have the intrinsic property to self-assemble and form higher-ordered macrostructures (nanotubes, Swiss-rolls, 2D sheets) when recombinantly expressed alone in E. coli. This peculiarity has already been exploited in multiple studies to create a protein scaffold for the immobilization of enzymes. In these proof-of-concepts, a sole BMC-H was used to build the scaffold, which would only permit to immobilized different enzymes in a random fashion.Here, we propose to go further with the idea of spatial organization and aimed to elaborate a protein platform starting from an hetero-hexamer. This hetero-hexamer would be composed by 2 up to 6 different BMC-H with each BMC-H constituting an anchoring point for a future enzymatic domain. With such platform, the spatial organization of the enzymes would be more finely controlled which would further enhance the catalysis efficiency of a metabolic pathway.To meet this goal, de novo designed BMC-H were created by 2 collaborator teams of computational design. I studied them and searched for BMC-H couples that would depict orthogonal intra-hexamer interfaces. Indeed, to be able to control precisely the organization onto the platform, this would require to ensure a specific BMC-H order within the hetero-hexamer and thus, tightly control which BMC-H is adjacent to which one and prevent any other association
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Valentová, Lucie. "Izolace a stanovení struktur proteinů: hexamerin potemníka Tribolium Castaneum a TmpH fága phi812." Master's thesis, Vysoké učení technické v Brně. Fakulta chemická, 2019. http://www.nusl.cz/ntk/nusl-401898.
Анотація:
Tato práce se zabývá strukturní studií dvou proteinů: proteinu Tail morphogenetic protein H (TmpH) bakteriofága 812, který napadá Zlatého stafylokoka (Staphylococcus aureus) a hexamerinu z potemníka (Tribolium castaneum). S. aureus je jedním z nejvíce rezistentních patogenů způsobující onemocnění s vysokou morbiditou a mortalitou. Bakteriofág 812 je schopen infikovat a lyzovat 95 % kmenů S. aureus a má potenciální využití ve fágové terapii. Protein TmpH je součástí virionu tohoto fága. V rámci této práce bylo připraveno několik plazmidů nesoucích gen TmpH, které byly použity pro rekombinantní expresi proteinu v buňkách E. coli BL21(DE3). Protein byl vyčištěn afinitní a gelovou chromatografií. Pro čistý protein byly optimalizovány krystalizační podmínky. Hexamerin je nejhojnějším proteinem larev a kukel hmyzu s dokonalou proměnou. V průběhu metamorfózy hexamerin slouží jako zdroj aminokyselin. V rámci této práce byl hexamerin izolován z kukel potemníka T. castaneum. Pro stanovení struktury hexamerinu byly použity dvě metody: rentgenová krystalografie a kryo-elektronová mikroskopie. Byly optimalizovány podmínky pro růst krystalů a vypěstovány krystaly vhodné pro sběr difrakčních dat. Nicméně struktura hexamerinu byla rychleji vyřešena kryo-elektronovou mikroskopií s rozlišením 3.2 . Znalost struktury hexamerinu umožní pochopení jeho funkce v regulaci vývoje hmyzu s dokonalou proměnou.
3
Reddy, Gangadasu E. C. V. Sagar. "Storage and utilization of hexamerin proteins in the pitcher plant mosquito, Wyomyia smithii by Gangadasu E.C.V. Sagar Reddy." Click here to access thesis, 2008. http://www.georgiasouthern.edu/etd/archive/fall2008/gangadasu_s_reddy/reddy_gangadasu_e_200808_ms.pdf.
Анотація:
Thesis (M.S.)--Georgia Southern University, 2008."A thesis submitted to the Graduate Faculty of Georgia Southern University in partial fulfillment of the requirements for the degree Master of Science." Directed by William S. Irby. ETD. Includes bibliographical references (p. 42-47) and appendices.
4
PIROVANO, LAURA. "NUMA:LGN HETERO-HEXAMERS PROMOTE THE ASSEMBLY OF CORTICAL PROTEIN NETWORK TO CONTROL PLANAR CELL DIVISIONS." Doctoral thesis, Università degli Studi di Milano, 2020. http://hdl.handle.net/2434/697169.
Анотація:
Mitotic spindle orientation is a prerequisite for the correct completion of mitosis, and is essential for tissue morphogenesis and maintenance. Divisions occurring within the plane of epithelia, or planar divisions, shape the architecture of epithelial sheets, whereas vertical divisions along the apicobasal axis are associated with asymmetric fate specification and stratification. Several studies described the evolutionary conserved trimeric Gi:LGN:NuMA complex as the core constituent of the spindle orientation machinery. In mitosis Gi:LGN:NuMA complexes localize at the cortex and orient the spindle by generating pulling forces on astral microtubules emanating from the spindle poles, via interaction of NuMA with the minus-end directed motor proteins dynein/dynactin. Biochemical and structural studies identified the minimal binding domains of the NuMA:LGN interaction, showing that a 30-residues stretch in the C-terminal part of NuMA binds to the inner groove formed by the eight TPR repeats at the N-terminus of LGN. However, how such interaction is organized at the cell cortex and triggers microtubules-motor activation still remains largely unclear. My PhD project focused on the characterization of the NuMA:LGN interaction and on the analysis of the role of the microtubule-binding domain of NuMA. Studies conducted during this thesis revealed that NuMA and LGN assemble in hetero-hexameric structures organized in a donut-shape architecture. In such arrangement, the LGN helices preceding and following the TPR repeats, and a NuMA motif preceding the shortest LGN-binding motif, are essential for the interaction. Consistently, an LGN oligomerization-deficient mutant cannot rescue misorientation defects caused in HeLa cells and Caco-2 three-dimensional cysts by endogenous LGN ablation. Importantly, in cells expressing the oligomerization-deficient mutant, force generators are correctly localized at the cell cortex. We provided evidence that LGN and NuMA assemble high-order oligomers in cells, and that the 3:3 stoichiometry of the NuMA:LGN complex combined with the dimeric state of NuMA coiled-coils promote the formation of a large proteins network. We also showed that ectopic targeting of an oligomerization-deficient NuMA mutant at the cortex is not sufficient to orient the spindle, indicating that the molecular organization of NuMA in complex with LGN is required to orient the spindle in metaphase. Furthermore, we provided evidence that the NuMA:LGN oligomers are compatible with the direct association of NuMA to microtubules, and that the microtubules-binding domain of NuMA is required to correctly localize NuMA at the poles and at the cortex, and to orient the spindle. Collectively, our findings suggest a model whereby cortical LGN:NuMA hetero-hexamers favor the accumulation of dynein motors at cortical sites. We speculate that direct binding of NuMA to astral microtubule plus-tips assists the processive movement of dynein along the depolymerizing astral microtubules to promote spindle placement.
5
Chakraborti, Srinjoy. "Therapeutic Antibody Against Neisseria gonorrhoeae Lipooligosaccharide, a Phase-variable Virulence Factor." eScholarship@UMMS, 2017. https://escholarship.umassmed.edu/gsbs_diss/905.
Анотація:
Neisseria gonorrhoeae (Ng) which causes gonorrhea has become multidrug-resistant, necessitating the development of novel therapeutics and vaccines. mAb 2C7 which targets an epitope within an important virulence factor, the lipooligosaccharide (LOS), is a candidate therapeutic mAb. Ninety-four percent of clinical isolates express the 2C7-epitope which is also a vaccine target.
Ng expresses multiple LOS(s) due to phase-variation (pv) of LOS glycosyltransferase (lgt) genes. mAb 2C7 reactivity requires a lactose extension from the LOS core Heptose (Hep) II (i.e. lgtG ‘ON’ [G+]). Pv results in HepI with: two (2-), three (3-), four (4-), or five (5-) hexoses (Hex). How HepI glycans impact Ng infectivity and mAb 2C7 function are unknown and form the bases of this dissertation.
Using isogenic mutants, I demonstrate that HepI LOS glycans modulate mAb 2C7 binding. mAb 2C7 causes complement (C’)-dependent bacteriolysis of three (2-Hex/G+, 4-Hex/G+, and 5-Hex/G+) of the HepI mutants in vitro. The 3-Hex/G+ mutant (resistant to C’-dependent bacteriolysis) is killed by neutrophils in the presence of mAb and C’. In mice, 2- and 3-Hex/G+ infections are significantly shorter than 4- and 5-Hex/G+ infections. A chimeric mAb 2C7 that hyperactivates C’, attenuates only 4- and 5-Hex/G+ infections.
This study enhances understanding of the role of HepI LOS pv in gonococcal infections and shows that longer HepI glycans are necessary for prolonged infections in vivo. This is the first study that predicts in vitro efficacy of mAb 2C7 against all four targetable HepI glycans thereby strengthening the rationale for development of 2C7-epitope based vaccines and therapeutics.
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Chakraborti, Srinjoy. "Therapeutic Antibody Against Neisseria gonorrhoeae Lipooligosaccharide, a Phase-variable Virulence Factor." eScholarship@UMMS, 2005. http://escholarship.umassmed.edu/gsbs_diss/905.
Анотація:
Neisseria gonorrhoeae (Ng) which causes gonorrhea has become multidrug-resistant, necessitating the development of novel therapeutics and vaccines. mAb 2C7 which targets an epitope within an important virulence factor, the lipooligosaccharide (LOS), is a candidate therapeutic mAb. Ninety-four percent of clinical isolates express the 2C7-epitope which is also a vaccine target.
Ng expresses multiple LOS(s) due to phase-variation (pv) of LOS glycosyltransferase (lgt) genes. mAb 2C7 reactivity requires a lactose extension from the LOS core Heptose (Hep) II (i.e. lgtG ‘ON’ [G+]). Pv results in HepI with: two (2-), three (3-), four (4-), or five (5-) hexoses (Hex). How HepI glycans impact Ng infectivity and mAb 2C7 function are unknown and form the bases of this dissertation.
Using isogenic mutants, I demonstrate that HepI LOS glycans modulate mAb 2C7 binding. mAb 2C7 causes complement (C’)-dependent bacteriolysis of three (2-Hex/G+, 4-Hex/G+, and 5-Hex/G+) of the HepI mutants in vitro. The 3-Hex/G+ mutant (resistant to C’-dependent bacteriolysis) is killed by neutrophils in the presence of mAb and C’. In mice, 2- and 3-Hex/G+ infections are significantly shorter than 4- and 5-Hex/G+ infections. A chimeric mAb 2C7 that hyperactivates C’, attenuates only 4- and 5-Hex/G+ infections.
This study enhances understanding of the role of HepI LOS pv in gonococcal infections and shows that longer HepI glycans are necessary for prolonged infections in vivo. This is the first study that predicts in vitro efficacy of mAb 2C7 against all four targetable HepI glycans thereby strengthening the rationale for development of 2C7-epitope based vaccines and therapeutics.
7
Xue, Yu Lord Susan T. "Study protein-protein interaction in methyl-directed DNA mismatch repair in E. coli exonuclease I Exo I and DNA helicas II UvrD; A minimal exonuclease domain of WRN forms a hexamer on DNA and possesses both 3'-5' exonuclease and 5'-protruding strand endonuclease activities; Solving the structure of the ligand-binding domain of the pregnane-xenobiotic-receptor with 17[beta] estradiol and T1317 /." Chapel Hill, N.C. : University of North Carolina at Chapel Hill, 2008. http://dc.lib.unc.edu/u?/etd,2015.
Анотація:
Thesis (Ph. D.)--University of North Carolina at Chapel Hill, 2008.Title from electronic title page (viewed Feb. 17, 2009). "... in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Department of Chemistry." Discipline: Chemistry; Department/School: Chemistry.
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Nagamanju, P. "Hexamerins, their gene and binding protein in rice moth, corcyra cephalonica." Thesis, 2003. http://hdl.handle.net/2009/883.
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Pantakani, Dasaradha Venkata Krishna. "Functional Characterization of Hereditary Spastic Paraplegia Proteins Spastin and ZFYVE27." Doctoral thesis, 2009. http://hdl.handle.net/11858/00-1735-0000-0006-B685-A.
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Palivec, Vladimír. "Počítačové modelování interakcí iont ů s proteiny: Allosterický efekt iont ů a fenolických ligand ů na strukturu insulinového hexameru." Master's thesis, 2016. http://www.nusl.cz/ntk/nusl-344126.
Анотація:
Title: Computer modeling of ion protein interactions: Allosteric effects of phenolic ligands and ions on insulin hexamer structure Author: Vladimír Palivec Department: Department of Physical and Macromolecular Chemistry Faculty of Science UK Advisor: prof. RNDr. Pavel Jungwirth, DSc., IOCB AS CR, v.v.i. Advisor's email address: pavel.jungwirth@uochb.cas.cz Abstract: Insulin hexamer is an allosteric protein capable of undergoing conformational changes between three states: T6, T3R3, and R6. Transitions between them, as well as the formation of insulin hexamers, are mediated through binding of phenolic ligands or ions. This thesis presents a molecular dynamics study of allosteric behavior of insulin using empirical force fields. Two effects are closely inspected - cation (Zn2+ , Ca2+ , K+ , and Na+ ) binding to the insulin hexamers and a possible binding of two neurotransmitters - dopamine and serotonin to the phenolic pocket. The results show that high charge density cations (Zn2+ and Ca2+ ) are mostly localized in the B13 glutamate cavity, slow- down diffusion, while preventing other cations from entering. In contrast, low charge density cations (Na+ and K+ ) do not have this effect. Concerning neurotransmitters, dopamine does not bind to the phenolic pocket whereas serotonin binds in a similar way like...
Частини книг з теми "Hexameric proteins":
1
Cooke, Roger. "Muscle myosin, skeletal." In Guidebook to the Cytoskeletal and Motor Proteins, 421–24. Oxford University PressOxford, 1999. http://dx.doi.org/10.1093/oso/9780198599579.003.00127.
Анотація:
Abstract Skeletal muscle myosin is a large hexameric protein with two globular heads and a long coiled-coif a-helical rod. A portion of the skeletal muscle myosin rod aggregates to form the core of the thick filament found at the centre of the muscle sarcomere. The globular heads contain sites for the interaction with both actin filaments and ATP, and it is this interaction which generates the force of muscle cells.
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Littlewood, Trevor D., and Gerard I. Evan. "Sequence-specific DNA binding by HLH proteins." In Helix-Loop-Helix Transcription Factors, 36. Oxford University PressOxford, 1998. http://dx.doi.org/10.1093/oso/9780198502487.003.0004.
Анотація:
Abstract Virtually all bHLH and bHLHZ proteins bind specifically to a consensus hexameric DNA sequence (CANNTG) known as the E box. E box sequences are often palindromic and contain identical half-sites, each of which may be bound by one component of the dimer. Although the central dinucleotides of the E box are usually GC or CG, exceptions have been noted. The preferred E box sequences bound by known HLH proteins are summarized in Table 3. It is of note that several independent HLH factors within one species often bind the same sequence, implying the existence of mechanisms for regulating precisely which HLH protein is bound to the E box in the control region of a given gene at any one time. Sometimes, this involves differential expression of iso-specific factors within specific cell lineages. Often, however, several bHLH/bHLHZ factors coexist within a cell. One possible mechanism dictating specificity of binding may reside in additional sequence specificities flanking the consensus E box element.
3
Silva, Jerson L., and Andrea T. Da Poian. "Pressure and Cold Denaturation of Proteins, Protein-DNA Complexes, and Viruses." In High Pressure Effects in Molecular Biophysics and Enzymology. Oxford University Press, 1996. http://dx.doi.org/10.1093/oso/9780195097221.003.0013.
Анотація:
The application of hydrostatic pressure provides a means of appraising interprotein and intraprotein interactions isothermally and makes it possible to sample partially folded conformations. A number of proteins exhibit cold denaturation and cold dissociation. We have used the combined effects of pressure and low temperature to promote dissociation or denaturation of single-chain proteins, oligomers, protein-DNA complexes, and viruses. In this article, we summarize results that have biological relevance. The dissociation and denaturation of the hexameric protein, allophycocyanin, are accomplished only when the temperature is decreased to —10 °C, indicating the entropic character of the folding and association reaction. The folding and dimerization of Arc repressor in the temperature range of 0—20 °C is also favored by a large positive entropy that counteracts an unfavorable positive enthalpy. On binding operator DNA, Arc repressor becomes extremely stable against denaturation. However, the Arc repressor-operator DNA complex is cold denatured at subzero temperatures under pressure. The entropy increases greatly when Arc repressor binds tightly to its operator sequence but not to a nonspecific sequence. The dissociation and denaturation of icosahedral viruses by pressure and low temperature also have been studied. The procapsid shells of bacteriophage P22 only dissociate by pressure at temperatures below 0 °C. On the other hand, the monomeric coat protein is very unstable toward pressure. Cowpea mosaic virus (CPMV) dissociates only in the presence of 1.0 M urea, at 2.5 kbar when the temperature is decreased to — 15°C. At temperatures close to — 20 °C, partial denaturation is obtained even in the absence of urea. The assembly of CPMV is related to large and positive variations or enthalpy and entropy, making the assembly of ribonucleoprotein components an entropy-driven process. We conclude that protein folding, protein association, and protein-DNA recognition seem to need positive entropy to occur. We are facing a puzzle in which a final, apparently more ordered state is achieved, a state that paradoxically has more entropy. In the last 20 years, several studies have described the cold denaturation of proteins (Brandts, 1964; Sturtevant, 1977; Privalov et al., 1986; Griko et al., 1988; Chen & Schellman, 1989, and as reviewed in Privalov, 1990). However, unlike thermal denaturation, cold denaturation is not well understood.
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Remigante, Alessia, Rossana Morabito, Sara Spinelli, Angela Marino, Silvia Dossena, and Michael Pusch. "VRAC Channels and the Cellular Redox Balance." In Human Physiology - Annual Volume 2023 [Working Title]. IntechOpen, 2023. http://dx.doi.org/10.5772/intechopen.109563.
Анотація:
Volume-regulated anion channels (VRAC) are mainly involved in the regulated transport of osmolytes such as ions or small organic compounds across the plasma membrane during anisosmotic cell swelling. However, they also play additional roles in various pathophysiological processes, such as the transport of metabolites and drugs, extracellular signal transduction and anti-cancer drug resistance. These channels are formed by heteromers of LRRC8 proteins, of which LRRC8A is the essential subunit that combines with its paralogs LRRC8B–E to form hexameric complexes. Despite the extensive research devoted to the understanding of VRACs functions, different aspects of these channels are still to be characterized in depth. In this chapter, recent findings concerning the involvement of VRAC channels in the cellular redox balance will be summarized. Also, their relevance as potential targets of antioxidant therapies will be discussed.
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Crampton, Donald J., and Charles C. Richardson. "Bacteriophage T7 gene 4 protein: A hexameric DNA helicase." In Energy Coupling and Molecular Motors, 277–302. Elsevier, 2003. http://dx.doi.org/10.1016/s1874-6047(04)80007-6.
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Itsathitphaisarn, Ornchuma, Richard A. Wing, William K. Eliason, Jimin Wang, and Thomas A. Steitz. "The Hexameric Helicase DnaB Adopts a Nonplanar Conformation during Translocation." In Structural Insights into Gene Expression and Protein Synthesis, 365–75. WORLD SCIENTIFIC, 2020. http://dx.doi.org/10.1142/9789811215865_0042.
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Dunn, Michael F., Richard Palmieri, Niels C. Kaarsholm, Melinda Roy, Robert W. K. Lee, Zbignew Dauter, Christopher Hill, and Guy G. Dodson. "THE 2-ZINC INSULIN HEXAMER IS A CALCIUM-BINDING PROTEIN." In Calcium-Binding Proteins in Health and Disease, 372–83. Elsevier, 1987. http://dx.doi.org/10.1016/b978-0-12-521040-9.50062-0.
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Papini, E., and J. L. Telford. "Vacuolating cytotoxin (Helicobacter pylori)." In Guidebook to Protein Toxins and Their Use in Cell Biology, 110–11. Oxford University PressOxford, 1997. http://dx.doi.org/10.1093/oso/9780198599555.003.0038.
Анотація:
Abstract VacA is a protein that when purified from the culture supernatant of Type I Helicobacter pylori strains (Leunk et al. 1988; Cover and Blaser 1992; Crabtree et al. 1992; Telford et al. 1994a; Marchetti et al. 1995) has a molecular weight between 600000-700000 Da. In the Electron microscope, the protein appears as flower-shaped hexamers and heptamers, formed by identical monomers (Fig. 1) (Lupetti et al. 1996}. The gene codes for a precursor polypeptide of 140000 Da (Telford et al. 1994b), of which the amino-terminal of 95000 Da forms the VacA monomer, while the carboxy-terminal region is involved in secretion of the toxin into the culture medium. Once secreted into the extracellular space, the 95 000 Dalton monomer can be proteolytically cleaved at a specific site, forming two subunits of 37 000 and 58 000 Da, that may represent the A and B subunits typical of the AB type of bacterial toxins. One of the subunits is presumed to be involved in binding the eukaryotic cell receptor and facilitating the toxin internalization. The other subunit is presumed to act on and inactivate a molecule of eukaryotic cells that regulates a crucial step of vesicle trafficking.
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Roy, Melinda, Robert Lee, and Michael F. Dunn. "1H FT NMR STUDIES OF THE Co3+-SUBSTITUTED HEXAMER: CHARACTERIZATION OF METAL ION BINDING TO THE GLU(B13) SITE." In Calcium-Binding Proteins in Health and Disease, 424–26. Elsevier, 1987. http://dx.doi.org/10.1016/b978-0-12-521040-9.50076-0.
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Menestrina, G., and M. Ferreras). "α-Toxin (Staphylococcus aureus)." In Guidebook to Protein Toxins and Their Use in Cell Biology, 10–12. Oxford University PressOxford, 1997. http://dx.doi.org/10.1093/oso/9780198599555.003.0004.
Анотація:
Abstract Staphylococcal a-toxin is an exotoxin with hemolytic, cytotoxic, dermonecrotic, and lethal activity (Thelestam and Blomqvist 1988; Bhakdi and Tranum-Jensen 1991). It is secreted by most pathogenic strains of S. aureus (commonly Wood 46) as a water-soluble polypeptide of 33 kD (293 amino acid residues, sequence accession number to the Swiss Prot databank: P09616 HLA-STAAU; corrections were published (Walker et al. 1992)). Its relevance as a virulence factor has been firmly established, at least in animal models. As outlined in Fig. 1, this toxin oligomerizes on the surface of mammalian cells (and liposomes) to form a membrane-embedded oligomer of about 220 kD, which appears in the electron microscope as a hollow cylinder protruding from the plane of the bilayer. It forms crystalline 2D layers on lipid membranes of either natural or artificial origin. From such arrays, a low-resolution three-dimensional map of the oligomer was obtained (Olofsson et al. 1988), suggesting it was a hexamer. However, more recent low-resolution X-ray analysis of microcrystals (Gouaux et al. 1994) provided evidence that the oligomer is actually an heptamer like the one formed by aerolysin from Aeromonas hydrophila.
Тези доповідей конференцій з теми "Hexameric proteins":
1
Stewart, Ross A., Natalie Tigue, Samantha Ireland, James Hair, Lisa Bamber, Michael Oberst, Rebecca Leyland, et al. "Abstract 561: MEDI1873: A novel hexameric GITRL fusion protein with potent agonsitic and immunomodulatory activities in preclinical systems." 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.am2016-561.
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Andrieux, A., M. H. Charon, G. Hudry-Clergeon, and G. Marguerie. "FIBRINOGEN SEQUENCES INTERACTING WITH PLATELET GPIIbIIIa." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643519.
Анотація:
Fibrinogen (Fg), fibronectin (Fn) and von Willebrand factor (vWF), interact with GPIIbllla on AD? stimulated platelets, and a common mechanism has been postulated for the binding of these adhesive proteins. Fg, Fn and vWF contain the tripeptide Arg-Gly-Asp and synthetic analogues to this sequence inhibit their interaction with platelet and their concomitant adhesive reactions. On the other hand, sequences corresponding to the Fg γ chain inhibit the binding of Fg, Fn and vWF to platelet and may also represent a potential recognition site. This raises the possibility that the γ chain sequence and Arg-Gly-Asp interact with the same site or represent primary and secondary sites for the Fg molecule. Within this context, the capacity of these sequences to interact with GPIIbllla and to block fibrinogen binding were compared. The smallest γ chain sequence that was active in inhibiting this reaction was the hexamer Lys-Gln-Ala-Gly-Asp-Val corresponding to the last six amino acid residues at the C-terminus of the γ chain. In parallel, peptides with the structure Arg-Gly-Asp-X were synthesized and tested in vitro. The activity of these peptides was dependent upon the hydrophobicity of the amino acid residue at position X. Arg-GLy-Asp-Phe corresponding to the sequence at position 95-98 in the Fg Aα chain was 5 to 10 times more active than Arg-GLy-Asp-Ser, present at position 572-575 in the Aα chain, and was 10 to 20 times more active than the γ chain hexamer. Both the Aα chain and γ chain sequences however, inhibited Fg binding by greater than 90%. When the γ chain sequence and the Arg-Gly-Asp-X sequence were coupled to Sepharose, GPIIbIIIa interacted with these sequences and was eluted from each column by either of the peptides. Finally direct binding experiments indicated that Arg-Gly-Asp-X and γ chain sequences are competitive antagonists. These results suggest that both sequences interact with the same site on GPIIbIIIa and comparison of the hydrophilicity of these peptides suggests that the binding domain on GPIIbIIIa exhibits hydrophobic properties.