STRUCTURES OF VON WILLEBRAND FACTOR AND ITS COMPLEXES WITH GLYCOPROTEIN LB AND A

血管性血友病因子及其与糖蛋白LB和A的复合物的结构

• 批准号: 8170164
• 负责人: Hua Jing
• 金额: $ 0.27万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8170164
• 关键词: Antibodies; Binding Sites; Blood Platelets; Cleaved cell; Complex; Computer Retrieval of Information on Scientific Projects Database; Crystallization; Data Collection; Funding; Glycoprotein Ib; Glycoproteins; Grant; Hemostatic function; Institution; Metalloproteases; Play; Process; Research; Research Personnel; Resources; Role; Screening procedure; Site; Source; Structure; Thrombin; Thrombosis; United States National Institutes of Health; numb protein; 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. Von Willebrand factor (VWF) plays a pivotal role in thrombosis and hemostasis. It is a polymeric multi-domain molecule, with a subunit of 250 kDa, which interacts with a number of proteins including its platelet receptor, glycoprotein (GP) Ib, and metalloproteinase ADAMTS-13, which specifically cleaves VWF. We propose to study crystal structures of VWF fragments both by themselves and in complex with GP-Ib and ADAMTS-13. We have obtained crystals of a central fragment of VWF, A1-A2-A3, in complex with the inhibitory antibody, NMC4. The A1 domain contains the binding site for the receptor GP-Ib, and the A2 domain contains the cleavage site recognized specifically by ADAMTS-13. The crystals of A1-A2-A3 and NMC4 complex were small and did not diffract. We are optimizing crystallization conditions and plan to bring larger crystals to SSRL for screening and data collection. We have also obtained the ternary complex of the amino terminal domain of GP Ib?, VWF-A1, and thrombin, and are in the process of performing crystallization screening.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 冯·威尔布兰德因子（VWF）在血栓形成和止血中起关键作用。它是一种聚合物多域分子，亚基为250 kDa，它与许多蛋白质相互作用，包括其血小板受体糖蛋白（GP）IB和金属蛋白酶ADAMTS-13，该蛋白质特异性地裂开了VWF。 我们建议自己研究VWF片段的晶体结构，并与GP-IB和ADAMTS-13复杂化。我们已经获得了与抑制性抗体NMC4复杂的VWF中心片段A1-A2-A3的晶体。 A1结构域包含受体GP-IB的结合位点，A2域包含ADAMTS-13专门识别的裂解位点。 A1-A2-A3和NMC4复合物的晶体很小，没有衍射。我们正在优化结晶条件，并计划将较大的晶体带到SSRL进行筛选和数据收集。我们还获得了GP IB的氨基末端结构域的三元复合物，VWF-A1和凝血酶，并且正在进行结晶筛选。