STRUCTURAL BASIS FOR VESICLE TRAFFICKING BY RAB GTPASES

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。次级项目的主要支助 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 为子项目列出的总成本可能 表示子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 主要目的是了解小GTP酶的Rab家族在活细胞中的囊泡运输途径的结构基础。 真核细胞是一个复杂的动态系统的亚细胞区室的组织和调节的小GTP酶。 Rabs是Ras超家族中最大的成员，有近70个基因，每个基因在活性（GTP结合）状态下定位于不同的亚细胞区室。 尽管有一个共同的折叠，Rabs招募他们的同源效应蛋白与精致的特异性。 效应子通常是模块化的，具有Rab-binding结构域（RBD）和施加生物学效应的另外的结构域，所述生物学效应例如细胞器结构和遗传，以及囊泡形成、运输、对接和融合。 效应蛋白的数量数以百计，绝大多数具有未知的三维结构。 随着二价效应物的鉴定，进一步的复杂性已经出现，所述二价效应物可以同时接合两个Rab，从而连接各种运输途径和亚细胞区室。 我们的研究计划是通过使用X射线晶体学可视化Rab-effector复合物来了解囊泡动力学的分子基础。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The principal aim is to understand the structural basis for vesicle trafficking pathways in living cells by the Rab family of small GTPases. Eukaryotic cells are a complex and dynamic system of subcellular compartments that are organized and regulated by small GTPases. Rabs comprise the largest member of the Ras superfamily with nearly 70 genes, each localized to a distinct subcellular compartment in the active (GTP-bound) state. Despite a common fold, Rabs recruit their cognate effector proteins with exquisite specificity. Effectors are typically modular, with a Rab-binding domain (RBD) and additional domains that exert biological effects such as organelle structure and inheritance, as well as vesicle formation, transport, docking and fusion. The population of effector proteins number in the hundreds, the vast majority with unknown three-dimensional structures. Further complexity has emerged with the identification of divalent effectors that can simultaneously engage two Rabs, thereby linking various trafficking pathways and subcellular compartments. Our research programme is to understand the molecular basis for vesicle dynamics by visualizing Rab-effector complexes using X-ray crystallography.