细胞整合素(integrin)激活蛋白kindlin的结构生物学研究

项目名称： 细胞整合素(integrin)激活蛋白kindlin的结构生物学研究

项目编号： No.31500621

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 生物科学

项目作者： 余聪

作者单位： 南方科技大学

项目金额： 21万元

中文摘要： 整合素（integrin）介导的细胞-细胞外基质（ECM）在细胞迁移、侵袭、繁殖等过程中发挥重要作用。Integrin介导“由外向内”和“由内向外”的双向信号传导。Kindlin蛋白被报道也可以通过结合integrin而激活integrin。Kindlin蛋白和许多疾病比如皮肤疾病、免疫系统的疾病相关，同时，在癌症细胞的生长和迁移中发挥重要作用。虽然kindlin蛋白被报道可以通过它的FERM结构域和integrinβ胞内区域的NPxY结构域直接结合，但是其中具体的分子机理人们还不清楚。在本项目中，我们采用结构生物学和生物化学的方法，研究kindlin蛋白和integrin相互作用的机理，从而了解kindlin蛋白在激活integrin过程中如何发挥重要作用。我们的研究将为理解kindlin在众多疾病中的作用提供帮助。

中文关键词： 复合物；蛋白质结构；相互作用；整合素

英文摘要： Integrin mediated cell-ECM (extracellular matrix) adhesion plays critical roles in different cellular processes, including cell migration, invasion, proliferation, and tumor metastasis. Integrin can be activated by matrix ligand proteins or intracellular protein such as talin, and thus mediates bidirectional signaling (inside-out and outside-in). Recently, a FERM-containing protein, kindlin was found to bind with integrin and mediate integrin activation. Kindlin family contains 3 highly conserved members: kindling-1,-2,-3, all of which contain FERM domains for protein-protein interactions. Kindlins have been reported to be involved in many diseases such as skin disease, immune system disease, and play important roles in cancer cell invasion and migration. Although kindlins directly interact with a conserved motif (“NPxY”) in integrinβvia their FERM domains, the detailed molecular mechanism governing the interaction remain elusive. Here, we propose to use structural and biochemical methods to study that how kindlins interact with integrinβto activate integrin. Our study will not only provide the molecular basis for kindling-mediated integrin activation, but also shed lights into the understanding of the diseases caused by kindlin mutations.

英文关键词： complex;protein structure;interaction;integrin