Structural Genomics on Membrane Proteins

膜蛋白的结构基因组学

基本信息

批准号：
8334048
负责人：
WAYNE A. HENDRICKSON
金额：
$ 312.29万
依托单位：
NEW YORK STRUCTURAL BIOLOGY CENTER
依托单位国家：
美国
项目类别：
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/8334048
关键词：
Advisory Committees Amino Acid Sequence Antibodies Bacteria Baculoviruses Binding Biochemistry Bioinformatics Biological Biology Cells Cloning Communities Crystallization Crystallography Data Deposition Detergents Development Diabetes Mellitus Escherichia coli Eukaryotic Cell FDA approved Family Future Genome Genomics Homeostasis Homologous Gene Homology Modeling Information Management Insecta Institution Laboratories Light Measurement Membrane Membrane Proteins Metabolic Diseases Methods Molecular Target Monoclonal Antibodies New York Organism Output Participant Peptide Sequence Determination Pharmaceutical Preparations Phase Principal Investigator Procedures Production Protein Structure Initiative Proteins Reagent Recombinant DNA Recombinants Research Personnel Robotics Screening procedure Seeds Sister Specialized Center Structure Synchrotrons System Technology Testing Work X-Ray Crystallography base beamline experience expression cloning improved innovation member operation organizational structure programs protein expression protein purification protein structure repository scale up structural biology structural genomics technology development vector

项目摘要

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.

该提案的总体目的是通过采用由专家研究人员团队的集体经验告知的结构基因组学方法来加速有关膜蛋白的结构信息。我们已经建立了纽约膜蛋白结构NYCOMP的联盟，以朝着这一目标共同努力。 NYCOMP现在是蛋白质结构计划（PSI-2）的第2阶段的专业中心。正如PSI生物学构成的那样，NYCOMP将在六个机构中构成12位主要研究人员。我们的结构确定管道将通过对所有已知序列的生物信息学分析选择目标，继续进行重组DNA克隆，细菌或真核细胞中的蛋白质表达以及中等高吞吐量的蛋白质纯化，然后继续通过X--继续确定X--的结构。射线晶体学。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级纯化来处理目标。成功的候选人分配给参与者实验室以进行扩展和结晶。结构的功能分析将通过计算和常规的实验生物化学进行。将通过包括辅助NYCOMP成员以及NYCOMPS生物学主题在内的生物群落的提名来确定目标，这些主题涉及对膜蛋白宇宙的阐明以及能量稳态和代谢性疾病的结构研究。技术开发计划将旨在提高管道效率和结果质量。该项目将设法优化产出并与PSI生物学网络以及其他膜蛋白结构工作有效地集成。