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GPCR Network

GPCR网络

基本信息

批准号：
8324098
负责人：
RAYMOND C STEVENS
金额：
$ 18.95万
依托单位：
SCRIPPS RESEARCH INSTITUTE, THE
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/8324098
关键词：
Address Adenosine A2A Receptor Adrenergic Agents Agonist Architecture Area Binding Sites Bioinformatics Biology Biomedical Research Cell Surface Receptors Collaborations Communities Community Outreach Complex Computer Simulation Core Facility Coupled Data Decision Making Deuterium Docking Educational workshop Enzymes Equilibrium Family Feedback G Protein-Coupled Receptor Genes G-Protein-Coupled Receptors Genes Genetic Variation Goals Guidelines Homologous Gene Human Human Genome Hydrogen Instruction Ion Channel Learning Ligand Binding Ligands Lipids Mass Spectrum Analysis Meleagris gallopavo Membrane Proteins Modeling Molecular Molecular Models NMR Spectroscopy Peptide Receptor Pharmaceutical Preparations Phylogenetic Analysis Physiological Process Production Property Protein Family Protein Structure Initiative Proteins Protocols documentation Publications Research Personnel Resolution Sampling Scientist Screening procedure Signal Transduction Site Solutions Structure System Technology Therapeutic Time Training Trees United States National Institutes of Health Visit adrenergic base cost experience extracellular human disease improved meetings member molecular modeling molecular recognition novel outreach preference protein expression protein purification protein structure receptor receptor binding response small molecule small molecule libraries structural biology success technology development tool

项目摘要

G protein-coupled receptors sense an astonishing variety of extracellular molecular signals and trigger complex intracellular and physiological responses. They share a common architecture of seven transmembrane helices connected by a broad range of intra- and extra-cellular loops and terminal domains. Structure determination feasibility of this protein family was demonstrated recently with the first high resolution studies on the human β2 adrenergic, turkey β1 adrenergic, and human adenosine A2A receptors. The Center for Membrane Protein Structure Determination (CMPD) has been created to use a protein family specific platform to determine the high resolution structures of 15-20 representative GPCRs distributed across the phylogenetic tree. Receptor structures are needed at a biologically relevant granularity, for small molecule ligand receptors, peptide and protein receptors, lipid receptors, class B-F receptors, and of receptors in the active and inactive functional states. Each receptor structure will be determined with a set of different pharmacological ligands to define the receptor binding site(s). Solution studies will be conducted with purified receptors bound to different ligands to understand receptor dynamics using hydrogen-deuterium exchange and NMR spectroscopy. In collaboration with the NIH screening center, a library of small molecule probes will be used to analyze each receptor and discover allosteric binding sites using a high throughput thermal stability screen. Through a biologically informed selection of representative receptors, we will maximize the CMPD‟s impact through computational modeling of close homologs and functional studies by external collaborators thereby establishing The PSI GPCR Network. The generated data will be provided to the community in a time frame consistent with the guidelines of the Protein Structure Initiative. Technology access will be achieved through on-site training, workshops, meetings, and publications. Processing access to the CMPD core facility will be provided through a 30% pipeline capacity commitment for the PSI:Biology Network nominated targets. Based on the experience of the CMPD investigators, preference will be for human or eukaryotic membrane proteins to maximally leverage the CMPD capabilities.

G蛋白偶联受体能感应到各种细胞外分子信号并触发