STRUCTURAL GENOMICS OF MEMBRANE PROTEINS

膜蛋白的结构基因组学

• 批准号: 8361717
• 负责人: Filippo Mancia
• 金额: $ 1.1万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-04-01 至 2012-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8361717
• 关键词: Area; Bacteria; Bacterial Proteins; Biological Process; Collaborations; Collection; Crystallization; Drug Design; Enzymes; Funding; Future; Grant; Homologous Gene; Laboratories; Membrane; Membrane Proteins; Methods; National Center for Research Resources; Neurobiology; New York; Peptide Hydrolases; Principal Investigator; Production; Protein Export Pathway; Proteins; Research; Research Infrastructure; Resources; Source; Structure; Structure-Activity Relationship; Synchrotrons; System; Transmembrane Transport; United States National Institutes of Health; cost; lipid metabolism; member; protein structure; relating to nervous system; structural biology; structural genomics; success; three dimensional structure

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).

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。子项目的主要支持 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。 列出的子项目总成本可能 代表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。 作为纽约膜蛋白结构协会（NYCOMPS）的成员，我们实验室的目标是确定一些原核生物膜蛋白的晶体结构。其中，细菌蛋白质输出系统的关键酶、与原核生物发生有关的转运系统、真核生物在中枢神经系统中表达的同源蛋白以及真核生物和细菌中脂质代谢的关键酶是我们近年来的研究重点。本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，或描述药物设计的潜在未来靶点。 除了开发成功进行蛋白质生产、纯化和结晶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关系，特别是与膜包埋蛋白酶、膜转运、神经生物学和脂质代谢领域的活跃团体。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，并且远远超出从结构基因组学方法发出的三维结构的简单集合。这些项目的晶体学分析主要在NE-CAT光束线24-ID-C和24-ID-E（阿贡国家实验室的APS同步加速器设施）上进行。