DOMAIN STRUCTURE OF PLATELET INTEGRIN IIB-IIIA

血小板整合素 IIB-IIIA 的结构域

• 批准号: 3432702
• 负责人: KENNETH C. INGHAM
• 金额: $ 2万
• 依托单位: AMERICAN NATIONAL RED CROSS
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-09-30 至 1996-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3432702
• 关键词: Escherichia coli; SDS polyacrylamide gel electrophoresis; calorimetry; chemical stability; divalent metal; gene expression; integrins; intermolecular interaction; ligands; peptide chemical synthesis; phase change; platelets; protein denaturation; protein folding; protein structure function; proteolysis; spectrometry; synthetic peptide; thermodynamics

Glycoprotein IIbIIIa is a heterodimeric integral membrane complex found on the surface of platelets and endothelial cells. A member of the integrin family of adhesion receptors, it plays an important role in blood clotting and wound healing. The goal of this research is to elucidate the structural and functional domain organization of IIbetaIIIalpha, to determine which parts of each subunit are independently folded and which parts are responsible for the various interactions. This will be accomplished through the preparation of fragments representing various parts of each subunit and examining their thermodynamic properties in comparison to those of the parent proteins through a combination of differential scanning calorimetry and spectroscopic methods. Those parts of each subunit which are involved in subunit interactions will be determined by evaluating the ability of the various fragments from one subunit to associate with the other subunit or its fragments. The interactions with divalent metal ions will be further characterized by measuring the effects of those ions on the stability of isolated domains and fragments. Knowledge of the domain structure of IIbetaIIIalpha will be helpful in understanding the molecular basis of diseases (such as Glanzmann's thrombasthenia) resulting from mutations in the genes coding for this receptor. Such knowledge will also serve as a guide to those who would attempt to use recombinant techniques to map the functions of this protein and other members of the integrin family.

糖蛋白IIbIIIa是一种异源二聚体整合膜复合物， 在血小板和内皮细胞的表面。 的成员 整合素家族的粘附受体，它发挥重要作用， 血液凝固和伤口愈合 这项研究的目的是 阐明结构和功能域组织 II β III α，以确定每个亚基的哪些部分是 独立折叠，哪些部分负责各种 交互. 这将通过编制 代表每个亚基的不同部分的片段，并检查它们的 与亲本蛋白质相比， 通过差示扫描量热法和 光谱方法 每个亚单位中参与 在亚基相互作用中，将通过评估 来自一个亚基的各种片段与另一个亚基结合 亚基或其片段。 与二价金属离子的相互作用将 通过测量这些离子对细胞的影响来进一步表征。 分离的结构域和片段的稳定性。 领域知识 II β III α的结构将有助于理解 疾病的分子基础（例如格兰兹曼血栓无力症） 由编码这种受体的基因突变引起。 等 知识也将作为那些试图使用 重组技术来定位这种蛋白质和其他蛋白质的功能， 整合素家族的成员。