CA BRIDGING MECHANISM & PHOSPHOLIPID HEAD GROUP RECOGNITION IN ANNEXIN V

CA桥接机制

• 批准号: 6123287
• 负责人: BARBARA A SEATON
• 金额: --
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-07-01 至 1999-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6123287
• 关键词: biological products; biomedical resource; human tissue; lipids; minerals; proteins; structural biology

Annexins are a family of cakcium- and phospholipid-binding proteins implicated in mediating membrane-related processes such as secretion, signal transduction, and ion channel activity. Structural evidence has been obtained for a Ca~'-bridging mechanism, proposed for Ca2'-binding interfacial membrane proteins such as annexins, protein kinase C, and certain coagulation proteins. Crystal structures of Ca~'-annexin V complexes with phospholipid polar heads provide molecular details of Ca~'-bridges as key features in the membrane attachment exhibited by these proteins. Distinct binding sites for phospholipid head groups are observed, including a novel, double-Ca~' recognition site for phosphoserine that may serve as a phosphatidylserine receptor site in vivo. We have solved the crystal structure of rat annexin V to 1.9 angstrom resolution by multiple isomorphous replacement. Unlike previously solved annexin V structures, all four domains bound calcium in this structure. Calcium binding in the third domain induced a large relocation of the calcium-binding loop regions, exposing the single tryptophan residue to the solvent. These alterations in annexin V suggest a role for domain 3 in calcium-triggered interaction with phospholipid membranes. Mass spectrometry experiments are being used to obtain profiles of the phospholipids associated with annexin V.

膜联蛋白是钙和磷脂结合的家族 参与介导膜相关过程的蛋白质，如 分泌、信号转导和离子通道活性。结构性 已经获得了钙桥联机制的证据，提出了 与Ca2‘结合的界膜蛋白，如膜联蛋白、蛋白质 激酶C和某些凝血蛋白。晶体结构的研究 具有磷脂极头的Ca~‘-Annexin V络合物提供 钙桥的分子细节是膜中的关键特征 这些蛋白质表现出的附着性。不同的结合位点 观察到磷脂头基团，包括一种新的双Ca~‘ 磷酸丝氨酸的识别位点可作为一种 磷脂酰丝氨酸受体在体内的位置。我们已经解开了水晶 大鼠膜联蛋白V结构的多重分辨至1.9埃 同构替换。与之前解决的Annexin V不同 结构，所有四个结构域都结合了这个结构中的钙。钙 第三个结构域中的绑定导致了 钙结合环区，暴露单一色氨酸残基 变成了溶剂。膜联蛋白V的这些变化表明 钙触发与磷脂膜相互作用的结构域3。 质谱学实验正在被用来 获得与膜联蛋白V相关的磷脂的图谱。