STRUCTURE/INTERACTION OF IGSF AND INTEGRIN FAMILIES

IGSF 和整合素家族的结构/相互作用

• 批准号: 6657106
• 负责人: JIA-HUAI WANG
• 金额: $ 31.05万
• 依托单位: IMMUNE DISEASE INSTITUTE, INC.
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-01 至 2003-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6657106
• 关键词: cell adhesion molecules; chemotaxis; inflammation; integrins; leukocyte adhesion molecules; protein binding; protein protein interaction; protein structure function; receptor binding; vascular endothelium

Adhesion of cells to other cells or to the cellular matrix is crucial in many biological processes. Leukocyte, in particular, is vital for the immune system. There are several adhesion molecule families, of which integrins are the most versatile. Because of their large size and complexity, there is little structural information available, compared to other adhesion molecule families. This proposal aims to determine the crystal structures of one integrin molecule (beta2 integrins or an "easy" integrins), or dissect one integrin by determining structures of its subunits and fragments. As a continuation from the previous grant period, we will also determine the structure of the whole extracellular portion of ICAM-1 (or ICAM-3 or ICAM-5) as well as a complex of binding domain from beta2- integrin with ligand such as fragment of ICAM-1, ICAM-2 or ICAM-3. We would like to eventually help unravel the mechanism of "inside-out" and "outside-in" signaling associated with these adhesion molecules from the structural point of view. This is extremely important for understanding how the adhesion is regulated in response to stimuli in various tissues. Finally we will also carry out structure analyses of the beta-propeller domain (the critical ligand-binding domain in integrin) from the extracellular portion of other cell surface proteins, such as nidogen, and even some bacterial proteins that contain beta-propellers very similar to those found in integrins. We would like to explore the evolutionary trial of the beta-propeller domain as an important module used in protein-protein interactions in various cell recognition processes.

细胞与其他细胞或细胞基质的粘附在许多生物过程中是至关重要的。特别是白细胞，对免疫系统至关重要。有几个粘附分子家族，其中整合素是最通用的。由于它们的大尺寸和复杂性，与其他粘附分子家族相比，几乎没有可用的结构信息。该提议旨在确定一种整联蛋白分子（β 2整联蛋白或“易”整联蛋白）的晶体结构，或通过确定其亚基和片段的结构来分解一种整联蛋白。作为上一个资助期的延续，我们还将确定ICAM-1（或ICAM-3或ICAM-5）的整个细胞外部分的结构以及β 2-整联蛋白与配体（如ICAM-1、ICAM-2或ICAM-3片段）的结合结构域的复合物。我们希望最终从结构的角度帮助解开与这些粘附分子相关的“由内而外”和“由外而内”的信号传导机制。这对于理解粘附如何响应于各种组织中的刺激而调节是极其重要的。最后，我们还将进行β-螺旋桨结构域（整合素中的关键配体结合结构域）的结构分析，这些结构域来自其他细胞表面蛋白质的细胞外部分，例如巢蛋白，甚至一些含有与整合素中发现的β-螺旋桨非常相似的β-螺旋桨的细菌蛋白质。我们希望探索β-螺旋桨结构域作为蛋白质相互作用中的重要模块在各种细胞识别过程中的进化试验。