STRUCTURE AND FUNCTION OF THROMBOSPONDIN

血小板反应蛋白的结构和功能

• 批准号: 3486145
• 负责人: THOMAS C DETWILER
• 金额: $ 10.38万
• 依托单位: SUNY DOWNSTATE MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-12-01 至 1991-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3486145
• 关键词: protein structure; thrombospondins

Thrombospondin (Tsp) is a 450 kDa protein with 3 disulfide-linked chains. It is secreted by platelets and certain cultured cells. It binds to cells and many different proteins; it may function as an adhesive or sub-cellular matrix protein. We have observed that Tsp i) has a conformation-sensitive thiol, ii) has an intrachain disulfide bond with a conformation-dependent stability, and iii) readily forms disulfide-linked complexes with other proteins and with other molecules of Tsp. I hypothesize that this reflects a dynamic function of Tsp as a covalent crosslinking protein. As a test of this hypothesis and for further characterization of Tsp, the number and locations of thiols and conformation-sensitive disulfide bonds will be determined, and the specificity for protein and for location of disulfide bonds for the thiol-disulfide exchange will be examined. The thiol-disulfide exchange was shown to have a pH optimum below 7 (8-10 would be predicted); this will be studied to determine if the pH dependence reflects a pH- dependent conformational change or the influence of another ionizable group on the dissociation of the thiol. Finally, attempts will be made to determine whether the thiol is necessary for Tsp binding to cells (including platelets), for its lectin activity or for platelet aggregation.

血小板传播（TSP）是450 kDa蛋白，具有3个二硫键连接 链。 它由血小板和某些培养的细胞分泌。 它 结合细胞和许多不同的蛋白质；它可能充当 粘合剂或细胞亚基质蛋白。 我们已经观察到 TSP i）具有构象敏感的硫醇，ii）具有内在 具有依赖构象的二硫键，III） 很容易与其他蛋白质形成二硫键连接的复合物， 与TSP的其他分子。 我假设这反映了 TSP作为共价交联蛋白的动态功能。 作为 检验该假设并为TSP的进一步表征 硫醇和构象敏感的数量和位置 将确定二硫键和蛋白质的特异性 以及用于二硫键交换的二硫键债券 将被检查。 硫醇 - 二硫化物的交换显示为 pH值低于7（预测8-10）；这将是 研究以确定pH依赖性是否反映了pH- 依赖的构象变化或另一个人的影响 硫醇解离的可离子组。 最后，尝试 将确定是否需要TSP的硫醇 结合细胞（包括血小板），其凝集素活性或 血小板聚集。