甘露糖受体家族蛋白的结构生物学研究

项目名称： 甘露糖受体家族蛋白的结构生物学研究

项目编号： No.31270772

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 生物科学

项目作者： 何勇宁

作者单位： 中国科学院上海生命科学研究院

项目金额： 80万元

中文摘要： 细胞表面受体是细胞与周围环境进行信息与物质交流的媒介，对维持正常的生理功能有着不可替代的作用。甘露糖受体家族是一类分布很广的细胞表面受体，参与多个生物学路径，尤其在免疫识别调控中起着非常重要的作用。目前已知的该家族成员包括: 甘露糖受体, DEC205, FcRY, Endo180, 磷脂酶A2受体等。其中，甘露糖受体和DEC205主要分布在巨噬细胞及树突状细胞表面，识别相应的配体并调控免疫应答。FcRY和Endo180分别是抗体和胶原蛋白的内吞转运受体。磷脂酶A2受体则参与对磷脂酶的调控。迄今为止该家族成员还没有较高分辨率的结构模型，结构信息的缺乏极大地限制了对该家族功能的深入理解。本项目拟在已有的研究基础上，运用包括电子显微镜三维重构在内的多种结构生物学技术，以及分子和细胞生物学手段，系统性地研究该受体家族蛋白的三维结构以及受体与配体的相互作用，从而揭示其识别和转运调控的分子机制。

中文关键词： 免疫受体；甘露糖受体家族；冷冻电镜；电子断层成像；受体配体相互作用

英文摘要： Cell surface receptors mediate the interactions between cell and the environment, which is critical for maintaining the regular physiological functions of organisms. Mannose receptor family members are expressed by many cell types and involved in various biological pathways, especially in the immune system. Current known members of this family include mannose receptor, DEC205, FcRY, Endo180 and PLA2R. Mannose receptor and DEC205 are expressed by immune cells such as marcophages and dendritic cells and can activate or suppress immunity by recognizing different antigens. FcRY and Endo180 are endocytotic receptors for antibody and collagen, respectively. PLA2R plays an important role in regulating the activity of PLA2 . Although a large amount of research has been published about mannose receptor family members, structural details of this family remain unknown. Based on our previous research, we propose to use three-dimensional electron microscopic reconstruction and X-ray crystallography in combination with molecular and cellular techniques to investigate the structures of this receptor family, thereby understanding the molecular mechanisms of receptor-ligand recognition, transport and regulation.

英文关键词： immune receptor；mannose receptor family；cryoEM；electron tomography；receptor-ligand interaction