Midwest Center for Membrane Protein Structural Dynamics

中西部膜蛋白结构动力学中心

基本信息

批准号：
7498602
负责人：
Eduardo A Perozo
金额：
$ 7.68万
依托单位：
UNIVERSITY OF CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-03-01 至 2010-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7498602
关键词：
ATP phosphohydrolase Acetylcholine Active Sites Address Algorithms Amino Acids Amyloid beta-Protein Precursor Anisotropy Antibodies Applied Genetics Archaea Architecture Area Arts Asses Attention Award Bacteria Bacteriorhodopsins Baculoviruses Behavior Binding Binding Proteins Biochemical Biochemical Reaction Biochemistry Biogenesis Biological Biological Process Biology Biomass Biophysics Catalysis Cell Nucleus Cells Charge Chemicals Chemistry Chicago Childhood Chromosome Pairing Class Classification Code Collaborations Communication Communities Complement Complex Computational algorithm Computing Methodologies Condition Consensus Contracts Copper Core Facility Couples Coupling Crystallization Crystallography Cytokine Receptors DNA DNA Sequence DNA Sequence Rearrangement Data Databases Decompression Sickness Denmark Detergents Deterioration Development Discipline Disease Disease Association Drosophila genus Drug Design Dyes Ecology Ecosystem Electron Spin Resonance Spectroscopy Electron Transport Electrons Electrophysiology (science)Elements End Point Endopeptidases Endpoint Determination Energy Transfer Energy-Generating Resources Engineering Environment Equilibrium Event Evolution Family Figs - dietary Fluorescence Fluorescence Microscopy Fluorescence Resonance Energy Transfer Fluorescence Spectroscopy Fogs Fostering Fourier Transform Free Energy Freedom Funding Gated Ion Channel Gene Amplification Gene Expression Gene Proteins Generations Genetic Genome Genomics Goals Grant Growth Health Heart Heavy Metals Histidine Homeostasis Hormones Hour Human Human Genetics Human Genome Hybrids Hydrolysis Illinois Image Individual Infection Insecta Institutes Institution Integral Membrane Protein Internet Investigation Investments Ion Channel Ions Isotope Labeling Kidney Knockout Mice Knowledge Label Laboratories Lanthanoid Series Elements Lead Leadership Length Libraries Library Services Life Lifting Ligand Binding Ligands Link Liposomes Liquid substance Location Macromolecular Complexes Magnetic Resonance Mammalian Cell Maps Measurable Measurement Measures Mediating Membrane Membrane Biology Membrane Potentials Membrane Proteins Membrane Structure and Function Meta-Analysis Metagenomics Metals Methionine Methodology Methods Microscopic Modeling Modification Molecular Molecular Biology Molecular Chaperones Molecular Conformation Molecular Genetics Molecular Machines Molecular Weight Molecular and Cellular Biology Monitor Motion Movement Multienzyme Complexes Muscle Mutagenesis Myosin ATPase NMR Spectroscopy Na(+)-K(+)-Exchanging ATPase Nature Nerve Neurobiology Neurotransmitter Receptor Noise Nuclear Nuclear Magnetic Resonance Nuclear Receptors Numbers Oligonucleotides Oocytes Operative Surgical Procedures Optical Methods Optics Organism Oxygen PTEN gene Panthera onca Participant Pathway interactions Pediatrics Peptide Hydrolases Peptides Performance Phage Display Pharmacology Phase Phosphatidylinositols Phosphoric Monoester Hydrolases Physical Chemistry Physics Physiologic pulse Physiological Processes Physiology Planets Play Polymerase Chain Reaction Positioning Attribute Post-Translational Protein Processing Potassium Channel Preparation Principal Investigator Process Production Prolactin Receptor Property Protein Analysis Protein Biochemistry Protein Biosynthesis Protein Conformation Protein Dynamics Protein Engineering Protein Region Proteins Proteolysis Proteome Psychological Techniques Publishing Pulse taking Pump Purple Membrane Purpose Range Rate Reaction Reagent Receptor Activation Regulation Relative (related person)Relaxation Reporter Reporting Research Research Infrastructure Research Institute Research Personnel Resolution Resource Allocation Resources Retinal Rhodopsin Roentgen Rays Role Sampling Scaffolding Protein Science Screening procedure Secondary to Secure Series Serine Services Shapes Side Signal Pathway Signal Transduction Simulate Site Site-Directed Mutagenesis Skeletal Muscle Solid Solutions Solvents Somatotropin Source Specific qualifier value Spectroscopy, Fourier Transform Infrared Spectrum Analysis Speed Spin Labels Staging Standards of Weights and Measures Statistical Mechanics Stimulus Stream Structural Protein Structure Support of Research Surface Synapses Synaptic Transmission System Systems Biology Techniques Technology Terbium Tertiary Protein Structure Testing Time Travel United States National Institutes of Health Universities Vertebral column Water Weight Work X-Ray Crystallography Yeasts amyloid precursor protein processing anticancer research aqueous base cell growth cell motility chemical addition chemical bond chemical synthesis combinatorial computer studies computerized tools concept conformational conversion covalent bond cytokine day density design design and construction electric field electrical measurement electron donor expectation experience feeding improved in vivo innovation insight interest ligand gated channel luminescence resonance energy transfer macromolecule magnetic field member metagenomic sequencing microbial community microorganism milligram millisecond molecular dynamics molecular recognition multidisciplinary mutant nanodevice nanomachine nanosecond nitroxyl novel novel strategies parallel computing particle patch clamp peptide chemical synthesis phosphorescence presenilin-1 programs protein expression protein folding protein function protein protein interaction protein purification protein structure quantum quantum chemistry receptor receptor function reconstitution research study response rhomboid scaffold secretase sensor simulation single molecule steroid hormone structural biology structural genomics success tetramethylrhodamine theories three dimensional structure tool trafficking voltage voltage gated channel water channel yeast two hybrid system

项目摘要

DESCRIPTION (provided by applicant): Membrane proteins play an essential role in controlling the movement of material and information in and out of the cell, in determining the flow and use of energy, as well as in triggering the initiation of numerous signaling pathways. To fulfill these roles, conformational and interaction dynamics exert a dominant influence on their functional behavior, for it is the interplay between structure and dynamics what ultimately defines their function. The Midwest Center for Membrane Protein Structural Dynamics (MMPSD) is proposed as a highly interactive, tightly integrated and multidisciplinary effort focused on elucidating the relationship between structure, free energy landscapes, dynamics and function. The MMPSD will be organized around multidisciplinary project teams with investigators from institutions clustered geographically inn [sic] the Midwest to maximize true interactive collaborations and an efficient exchange of ideas. These teams will study major mechanistic questions associated with membrane protein function as it relates to three major areas: energy transduction in signaling (ion channels and receptors) energy interconversion (transporters and pumps) and chemo-transduction pathways (membrane-embedded proteases and phosphatases). Our ultimate goals is to decode the general mechanistic principles that govern protein movement and its associated fluctuation dynamics by dissecting and analyzing the molecular and dynamical bases of these functions at an unprecedented and quantitative level, as well as exploiting this information to engineer altered and novel activities into membrane protein frameworks to rationally evolve new functions. To accomplish its goals, the MMPSD will develop in parallel a set of tools, concepts and reagents to: 1) Determine time-averaged structures of "Archetype" membrane proteins using Chaperone-assisted crystallization methods; 2) Apply state of the art spectroscopic methods (Magnetic Resonance, Fluorescence) to follow conformational changes and dynamics of the determined structures; and 3) Design and implement novel computational approaches to link static and dynamic data with function. Four core facilities will feed and interconnect with the individual projects in a highly interactive way. The cores will support the research in the Center by providing service and expertise in four critical areas: Membrane protein expression, the establishment of chemical synthesis capabilities for probes and detergents, the generation of a large variety of crystallization chaperones and other target binders, and generation of a pipeline of novel membrane targets through metagenomics approaches. All of the information, tools and new reagents/targets will be shared with the research community at large through the "membrane protein dynamics gateway", a state of the art web page and a series of scientific meetings open to the public.

描述（由申请人提供）：膜蛋白在控制物质和信息进出细胞的运动、确定能量的流动和使用以及触发众多信号传导途径的启动方面发挥着重要作用。为了履行这些作用，构象和相互作用动力学对其功能行为产生主导影响，因为结构和动力学之间的相互作用最终定义了它们的功能。中西部膜蛋白结构动力学中心 (MMPSD) 是一个高度互动、紧密集成和多学科的机构，致力于阐明结构、自由能景观、动力学和功能之间的关系。 MMPSD 将围绕多学科项目团队进行组织，研究人员来自分布在中西部地区的机构，以最大限度地实现真正的互动合作和有效的思想交流。这些团队将研究与膜蛋白功能相关的主要机制问题，因为它涉及三个主要领域：信号传导中的能量转导（离子通道和受体）、能量相互转换（转运蛋白和泵）和化学转导途径（膜嵌入的蛋白酶和磷酸酶）。我们的最终目标是通过在前所未有的定量水平上剖析和分析这些功能的分子和动力学基础，以及利用这些信息来设计改变的和新颖的活动，来解码控制蛋白质运动及其相关波动动力学的一般机械原理。进入膜蛋白框架以合理地进化新功能。为了实现其目标，MMPSD 将同时开发一套工具、概念和试剂，以： 1) 使用分子伴侣辅助结晶方法确定“原型”膜蛋白的时间平均结构； 2) 应用最先进的光谱方法（磁共振、荧光）来跟踪所确定结构的构象变化和动力学； 3）设计和实现新颖的计算方法，将静态和动态数据与功能联系起来。四个核心设施将以高度互动的方式为各个项目提供支持和互连。这些核心将通过在四个关键领域提供服务和专业知识来支持该中心的研究：膜蛋白表达、探针和去污剂化学合成能力的建立、多种结晶伴侣和其他目标结合物的生成以及生成通过宏基因组学方法开发一系列新型膜靶标。所有信息、工具和新试剂/靶标将通过“膜蛋白动力学网关”、最先进的网页和一系列向公众开放的科学会议与整个研究界共享。