Structural Genomics of Membrane Proteins

膜蛋白的结构基因组学

• 批准号: 7090141
• 负责人: WAYNE A. HENDRICKSON
• 金额: $ 321.85万
• 依托单位: NEW YORK STRUCTURAL BIOLOGY CENTER
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-01 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7090141
• 关键词: X ray crystallography; biomedical resource; cooperative study; functional /structural genomics; membrane proteins; protein structure; proteomics

DESCRIPTION (provided by applicant): The overall objective of this proposal is to accelerate the acquisition of structural information about membrane proteins by applying a structural genomics approach informed by experience gained in studies driven by biological and biochemical problems. We propose to establish the New York Consortium on Membrane Protein Structure (NYCOMPS) to work collectively toward this objective. A pipeline for structure determination will be established starting from a bioinformatics analysis of all known sequences, moving on to recombinant cloning, protein expression and protein purification at moderate throughput, and then into structure determination by x-ray crystallography and NMR spectroscopy. A Protein Production Facility will be established in laboratories of the New York Structural Biology Center (NYSBC), and other activities will be carried out in the laboratories of NYCOMPS participants. We build on experience gained in addressing the structural biology of membrane protein structure in our own laboratories and from our participation in two pilot projects of the Protein Structure Initiative, the Northeast Structural Genomics Consortium (NESG) and the New York Structural Genomics Research Consortium (NYSGXRC). We also propose to conduct research aimed at improving the process, carried out both in the Protein Production Facility and also in several of the laboratories of participants. Milestones have been set for an initial exponential increase in structural output followed by linear growth later in the course of this five-year project. We expect that structural results from this initiative will provide greater biological insight for proteins having a putative function, afford an opportunity for biological discovery for those of unknown function, and give a deeper understanding of biophysical principles that underlie membrane protein structure generally. Methods derived in this work will also return benefits to our individual studies on well characterized biological problems.

描述（由申请人提供）：该提案的总体目标是通过应用结构基因组学方法来加速获取有关膜蛋白的结构信息，该方法是根据生物和生化问题驱动的研究中获得的经验而获得的。我们建议建立纽约膜蛋白结构联盟（NYCOMPS），共同努力实现这一目标。结构确定的流程将从所有已知序列的生物信息学分析开始，以中等通量进行重组克隆、蛋白质表达和蛋白质纯化，然后通过 X 射线晶体学和核磁共振波谱进行结构确定。纽约结构生物学中心（NYSBC）的实验室将建立蛋白质生产设施，其他活动将在NYCOMPS参与者的实验室进行。我们借鉴了在我们自己的实验室中解决膜蛋白结构生物学问题以及参与蛋白质结构计划、东北结构基因组学联盟 (NESG) 和纽约结构基因组学研究联盟 (NYSGXRC) 两个试点项目所获得的经验。 ）。我们还建议进行旨在改进工艺的研究，在蛋白质生产设施和参与者的几个实验室中进行。在这个五年项目的过程中，结构性产出最初呈指数增长，随后呈线性增长，已设定了里程碑。我们期望这一举措的结构结果将为具有假定功能的蛋白质提供更深入的生物学见解，为未知功能的蛋白质提供生物学发现的机会，并更深入地理解膜蛋白结构的生物物理原理。这项工作中得出的方法也将为我们对明确表征的生物学问题的个人研究带来好处。