Structure Function Correlation of G-Proteins

G 蛋白的结构功能相关性

• 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

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.

本研究的目的是探索g蛋白作用的一般分子基础。这将包括：a)继续研究催化Gln61在RasGAP系统中的作用，并将其扩展到其他相关系统，如Gas， Gia1和RanGAP，其中相关的谷氨酰胺残基起主要的催化作用。b)对不同g蛋白的作用进行比较研究，重点是转导蛋白、EF-Tu、Gas和Gia1。c)建立g蛋白与TS类似物复合物（tas）结构与实际过渡态（TSs）结构之间的关系。d)开展f1 - atp酶的机制和能量学研究。e)检测Ras/Raf系统中蛋白-蛋白相互作用对信号转导的影响。G蛋白及其附属蛋白的结构信息的可用性为更全面地了解控制信号转导的因素提供了独特的机会。这需要一个定量的结构函数关联，可以将可用的结构信息转换为活化能，从而转换为相关的速率常数和催化效应。本项目的目的是进一步发展这种相关性，探索信号转导G蛋白和F1-ATPase等能量转导蛋白的一般机制。这些研究有望促进对生物学中磷酸化转移的本质的理解以及对信号转导的分子细节的理解。