Structural Genomics on Membrane Proteins

膜蛋白的结构基因组学

• 批准号: 8146893
• 负责人: WAYNE A. HENDRICKSON
• 金额: $ 311.47万
• 依托单位: NEW YORK STRUCTURAL BIOLOGY CENTER
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-30 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8146893
• 关键词: Structural; Genomics; Membrane; Proteins

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 the collective experience of a team of expert investigators. We have established the New York Consortium on Membrane Protein Structure NYCOMPS to work together toward this objective. NYCOMPS participates as a Specialized Center in Phase 2 of the Protein Structure Initiative (PSI-2) now. As constituted for PSI-Biology, NYCOMPS will comprise 12 Principal Investigators at six institutions. Our pipeline for structure determination will select targets through a bioinformatics analysis of all known sequences, move on to recombinant DNA cloning, protein expression in bacteria or eukaryotic cells, and protein purification at moderately high throughput, and then continue on to determine structures by x-ray crystallography. Our Protein Production Facility at the New York Structural Biology Center (NYSBC) handles targets through purification at a mid-scale level; and successful candidates are distributed to participant laboratories for scale-up and crystallization. Functional analysis of structures will be performed both by computations and through routine experimental biochemistry. Targets will be identified through nominations from the biological community, including adjunct NYCOMPS members, and from NYCOMPS biological themes, which concern elucidation of the membrane protein universe and structural studies on energy homeostasis and metabolic disorders. A program in technology development will aim to improve pipeline efficiency and quality of results. The project will be managed to optimize output and to integrate effectively with the PSI-Biology network and with other membrane protein structure efforts.

这项建议的总体目标是通过应用结构基因组学方法，根据专家研究小组的集体经验，加快获取有关膜蛋白的结构信息。我们已经成立了纽约膜蛋白结构联盟NYCOMPS，为实现这一目标而共同努力。NYCOMPS现在作为一个专门的中心参与蛋白质结构倡议(PSI-2)的第二阶段。作为PSI-Biology的组成部分，NYCOMPS将由六个机构的12名首席调查人员组成。我们的结构确定流水线将通过对所有已知序列的生物信息学分析来选择目标，然后进行重组DNA克隆、在细菌或真核细胞中表达蛋白质，以及以适度高通量进行蛋白质纯化，然后继续通过X射线结晶学确定结构。我们位于纽约结构生物学中心(NYSBC)的蛋白质生产设施通过中等规模的纯化来处理靶标；成功的候选者被分发到参与实验室进行放大和结晶。结构的功能分析将通过计算和常规的实验生物化学来进行。目标将通过生物界的提名来确定，包括NYCOMPS的附属成员，以及NYCOMPS的生物主题，这些主题涉及膜蛋白宇宙的阐明以及关于能量稳态和代谢紊乱的结构研究。一项技术开发计划将旨在提高管道效率和结果质量。将对该项目进行管理，以优化产出，并有效地与PSI-Biology网络和其他膜蛋白质结构努力相结合。