Structure Function Correlation of G-Proteins

G 蛋白的结构功能相关性

基本信息

批准号：
0342276
负责人：
Arieh Warshel
金额：
$ 56.5万
依托单位：
University of Southern California
依托单位国家：
美国
项目类别：
Continuing Grant
财政年份：
2004
资助国家：
美国
起止时间：
2004-07-01 至 2009-06-30
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=0342276&HistoricalAwards=false
关键词：
Structure Function Correlation Proteins

项目摘要

The objective of this research is to explore the general molecular basis for the action of G-proteins. This will include: a) continuing studies of the role of the catalytic Gln61 in the RasGAP system and extending it to other related systems such as Gas, Gia1, and RanGAP, where related glutamine residues play a major catalytic role. b) Conducting a comparative study of the action of different G-proteins, focusing on transducin, EF-Tu, Gas and Gia1. c) Establishing the relationship between the structures of complexes of G-proteins and TS analogues (TSAs) and the structure of actual transition states (TSs). d) Conducting studies of the mechanism and energetics of F1-ATPase. e) Examining the effect of protein-protein interaction on signal transduction in the Ras/Raf system.The availability of structural information about G proteins and their accessory proteins offers a unique opportunity for a more complete understanding of the factors that control signal transduction. This requires a quantitative structure function correlation that can convert the available structural information to activation energies and therefore to the relevant rate constants and catalytic effects. The objective of this project is to further develop such correlations and explore the general mechanism of signal transducing G proteins and energy transducing proteins like F1-ATPase. These studies are expected to advance the understanding of the nature of phosphoryl transfer in biology as well as the understanding of the molecular details of signal transduction.

这项研究的目的是探索G蛋白作用的一般分子基础。这将包括：a）对催化GLN61在RasGAP系统中的作用的持续研究，并将其扩展到其他相关系统，例如GAS，GIA1和RAGAP，其中相关的谷氨酰胺残基起着主要的催化作用。 b）对不同G蛋白的作用进行比较研究，该研究的重点是转杜氏度，EF-TU，GAS和GIA1。 c）建立G蛋白与TS类似物（TSA）的复合物结构与实际过渡态（TSS）的结构之间的关系。 d）进行F1-ATPase的机理和能量学研究。 e）检查蛋白质 - 蛋白质相互作用对RAS/RAF系统中信号转导的影响。有关G蛋白及其辅助蛋白的结构信息的可用性为更完整地理解控制信号转导的因素提供了独特的机会。这需要定量结构函数相关性，可以将可用的结构信息转换为激活能，从而转换为相关的速率常数和催化效应。该项目的目的是进一步发展这种相关性，并探讨信号转导G蛋白和能量转导的蛋白质（如F1-ATPase）的一般机制。这些研究有望提高对生物学中磷酸转移的性质的理解，以及对信号转导的分子细节的理解。