GLYCOPROTEINS IN AXILLARY GLANDS

腋窝中的糖蛋白

• 批准号: 6478969
• 负责人: GEORGE PRETI
• 金额: $ 5.36万
• 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/6478969
• 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蛋白家族， 参与介导膜相关过程的蛋白质， 分泌、信号转导和离子通道活性。 结构 已经获得了Ca ~（2+）桥连机制的证据， Ca 2 '结合界面膜蛋白，如膜联蛋白、蛋白质 激酶C和某些凝固蛋白。 晶体结构 具有磷脂极性头的Ca ~（2+）-膜联蛋白V复合物提供了 钙桥的分子细节作为膜中的关键特征 这些蛋白质所表现出的附着力。 不同的结合位点， 磷脂头部基团，包括一个新的，双Ca ~' 磷酸丝氨酸的识别位点，可以作为 磷脂酰丝氨酸受体位点。 我们已经破解了水晶 大鼠膜联蛋白V结构多重分辨1.9埃 同晶置换 不像以前解决的膜联蛋白V 结构中，所有四个结构域都在该结构中结合钙。 钙 在第三个结构域的结合诱导了大的迁移， 钙结合环区域，暴露单个色氨酸残基 到溶剂。 膜联蛋白V的这些改变表明， 结构域3与磷脂膜的钙触发相互作用。 质谱实验被用来 获得与膜联蛋白V相关的磷脂谱。