GLYCOPROTEINS IN AXILLARY GLANDS

腋窝中的糖蛋白

• 批准号: 6345245
• 负责人: GEORGE PRETI
• 金额: $ 0.62万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-07-01 至 2002-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6345245
• 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家族 参与介导膜相关过程的蛋白质，例如 分泌、信号转导和离子通道活性。 结构性 已经获得了 Ca~'-桥接机制的证据，提出了 Ca2' 结合界面膜蛋白，例如膜联蛋白、蛋白质 激酶 C 和某些凝血蛋白。 晶体结构 具有磷脂极性头的 Ca~'-annexin V 复合物提供 Ca~'-桥的分子细节作为膜的关键特征 这些蛋白质表现出的附着力。 不同的结合位点 观察到磷脂头基，包括一个新的双 Ca~' 磷酸丝氨酸的识别位点，可作为 体内磷脂酰丝氨酸受体位点。 我们已经解决了水晶 大鼠膜联蛋白 V 的结构通过多重分辨率达到 1.9 埃 同晶置换。 与之前解决的膜联蛋白 V 不同 结构，所有四个结构域都在此结构中结合钙。 钙 第三个结构域的结合引起了大的重新定位 钙结合环区域，暴露单个色氨酸残基 至溶剂。 膜联蛋白 V 的这些改变表明了 结构域 3 参与钙触发的与磷脂膜的相互作用。 质谱实验被用来 获得与膜联蛋白 V 相关的磷脂的概况。