STRUCTURAL GENOMICS OF MEMBRANE PROTEINS

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 作为纽约膜蛋白结构联合会(NYCOMPS)的成员，我们实验室的目标是确定一些原核膜蛋白的晶体结构。其中包括细菌蛋白输出系统的关键酶、与原核生物致病相关的转运系统、中枢神经系统表达的真核同源蛋白以及真核细菌和真核生物中脂代谢的关键酶。这项研究的总体目标是阐明这些蛋白质的结构-功能关系，以加深我们对基本生物学过程的理解，或描述未来药物设计的潜在靶点。 除了开发在蛋白质生产、纯化和结晶方面取得成功所需的所有相关方法外，我们还在纽约地区建立了广泛的合作，特别是与活跃在膜嵌入蛋白酶、膜运输、神经生物学和脂类代谢领域的小组。这将使我们能够将我们的研究扩展到对这些系统的详细功能理解，而不仅仅是从结构基因组学方法发布的简单的三维结构集合。这些项目的结晶学分析主要是在东北-CAT束线24-ID-C和24-ID-E(Argonne国家实验室的APS同步加速器设施)上进行的。

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. As a participating member of the New York Consortium On Membrane Protein Structures (NYCOMPS), our laboratory aims at determining the crystallographic structures of some prokaryotic membrane proteins. Among them, we recently focused our efforts on key enzymes of bacterial protein export system, transport systems relevant to prokaryotic patogenicity, proteins with eukaryotic homologues expressed in the central neural system and key enzymes of lipid metabolism in both eukarya and bacteria. The overall objective of this studies is to elucidate structure-function relationship for these proteins, in order to sharpen our understanding of fundamental biological processes, or to describe potential future targets for drug design. Besides developing all the relevant methods necessary for success in protein production, purification and crystallization, we have established wide collaborations in the New York area, particularly with groups active in the fields of membrane embedded proteases, membrane transport, neurobiology and lipid metabolism. This will allow us to extend our study to a detailed functional understanding of these systems, and well beyond a simple collection of three-dimensional structures issued from a structural genomics approach. Crystallographic analysis of these projects is mostly taking place at the on the NE-CAT beam lines 24-ID-C and 24-ID-E (APS synchrotron facility at Argonne National Laboratory).