DOMAIN STRUCTURE OF PLATELET INTEGRIN IIB-IIIA

糖蛋白IIbIIIa是一种异二聚体的完整膜复合体 在血小板和血管内皮细胞表面。该委员会的成员 整合素家族的黏附受体，它在 血液凝结和伤口愈合。这项研究的目标是 阐明的结构和功能域组织 IIbetaIIIpha，以确定每个亚基的哪些部分 独立折叠以及由哪些部件负责各种 互动。这将通过准备 代表每个亚基的不同部分的片段并检查其 与亲本蛋白质的热力学性质的比较 通过差示扫描量热法和 光谱方法。每一亚单位所涉及的部分 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相关联 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 分离结构域和片段的稳定性。该领域的知识 IIbetaIIIpha的结构将有助于理解 疾病的分子基础(如Glanzmann‘s血栓减少症) 由编码该受体的基因突变所致。是这样的 知识也将成为那些试图使用 利用重组技术绘制该蛋白质和其他蛋白质的功能图谱 整合素家族的成员。

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.