K I VARUGHESE PRT TIME

基瓦鲁盖塞 PRT 时间

• 批准号: 7597932
• 负责人: KOTTAYIL I VARUGHESE
• 金额: $ 0.02万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-03-01 至 2008-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7597932
• 关键词: Adhesives; Affinity; Antihemorrhagics; Binding; Biological Process; Blocking Antibodies; Blood Platelets; Complex; Computer Retrieval of Information on Scientific Projects Database; Funding; Glycoproteins; Grant; Hemorrhage; Institution; Ligand Binding; Mediating; Mutation; Nature; Proteins; Regulation; Research; Research Personnel; Resolution; Resources; Source; Structure; Time; United States National Institutes of Health; alpha helix; botrocetin; mutant; receptor; von Willebrand Factor

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The presence of one or more copies of von Willebrand factor type A domain identifies a superfamily of proteins usually involved in biological processes controlled by specific molecular interactions, often adhesive in nature. We have solved the crystal structure of the prototypic von Willebrand factor A1 domain, essential for the antihemorrhagic activity of platelets, in complex with the function blocking antibody, NMC-4, at 2.2 ¿ resolution. This has led to the recognition of a putative binding groove for the platelet receptor, glycoprotein Iba, formed by two adjacent alpha-helices and a beta-strand. The structure also shows a contact interface between A1 domain pairs, suggesting a hypothetical mechanism for the regulation of protein assembly and heterologous ligand binding mediated by homophilic interactions of type A domains. The binding of the A1 domain to the glycoprotein Iba is essential to arrest bleeding. Certain mutations on the A1 domain abolish bleeding. Certain other mutations increase the affinity of binding. Studying the structures of these mutants and the structure of the modulator botrocetin will be the focus of this proposal.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以出现在其他 CRISP 条目中 列出的机构是。 对于中心来说，它不一定是研究者的机构。 冯维勒布兰德因子 A 型结构域的一个或多个拷贝的存在识别了通常参与由特定分子相互作用控制的生物过程的蛋白质超家族，这些相互作用通常具有粘性。我们已经解决了原型冯维勒布兰德因子 A1 结构域的晶体结构，对于血小板的抗出血活性至关重要，与功能阻断抗体 NMC-4 复合，浓度为 2.2 ¿这导致了血小板受体糖蛋白 Iba 的假定结合凹槽的识别，该凹槽由两个相邻的 α 螺旋和 β 链形成。该结构还显示了 A1 结构域对之间的接触界面，表明了一种假设的机制。 A1 结构域与糖蛋白 Iba 的结合对于抑制出血至关重要。研究这些突变体的结构和调节剂 botrocetin 的结构将是本提案的重点。