Calcium-Dependent Homophilic Interactions of E-Cadherin

E-钙粘蛋白的钙依赖性同质相互作用

• 批准号: 0212669
• 负责人: Susan Pedigo
• 金额: $ 36.75万
• 依托单位: University of Mississippi
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-01 至 2006-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0212669&HistoricalAwards=false
• 关键词: Calcium; Dependent; Homophilic; Interactions; Cadherin

Cell adhesion is responsible for the formation of tissues and organs. Cadherins are proteins that confer specificity to cells such that they adhere only to specific cell types. They are membrane-bound calcium-binding proteins with independently folded extracellular domains that participate in the cell-cell interactions. Calcium binds at the interface between the extracellular domains and changes their relative disposition. Calcium is required for cell adhesion. Studies of cadherins fall into two main categories, cellular level studies and high-resolution structural studies. Results from these approaches have not yielded a paradigm for the structural basis of the intermolecular interactions. At this point there is little understanding of the energetics of the molecular interactions involving cadherins. This project includes the study of the stability and calcium-binding properties of the extracellular domains of epithelial cadherin. In addition, the project will address how the calcium-binding properties depend on dimerization. These studies will elucidate the energetic origins of the calcium-linked interactions of cadherin that are critical for cell adhesion. The specific aims of this research are: characterization of the stability of the extracellular domains of epithelial-cadherin (ECAD12), determination of affinity and cooperative interactions for calcium binding to the sites between ECAD12, and establishing conditions under which cis-dimerization occurs for ECAD12. This project will have a broad positive impact on undergraduate and graduate education in physical biochemistry.

细胞粘附负责组织和器官的形成。 钙粘蛋白是赋予细胞特异性的蛋白质，使得它们仅粘附于特定的细胞类型。 它们是膜结合的钙结合蛋白，具有独立折叠的胞外结构域，参与细胞-细胞相互作用。 钙结合在细胞外结构域之间的界面处并改变它们的相对配置。 钙是细胞粘附所必需的。钙粘蛋白的研究主要分为两大类，细胞水平的研究和高分辨率结构的研究。 从这些方法的结果还没有产生一个范例的分子间相互作用的结构基础。 在这一点上，有很少的理解涉及钙粘蛋白的分子相互作用的能量。 本计画包括上皮钙黏蛋白胞外区之稳定性及钙结合特性之研究。此外，该项目将解决钙结合特性如何依赖于二聚化。 这些研究将阐明对细胞粘附至关重要的钙粘蛋白的钙连接相互作用的能量来源。本研究的具体目的是：表征上皮钙粘蛋白（ECAD 12）的胞外结构域的稳定性，确定ECAD 12之间的位点的钙结合的亲和力和合作相互作用，并建立ECAD 12发生顺式二聚化的条件。该项目将对物理生物化学的本科生和研究生教育产生广泛的积极影响。