Structure Function Correlation of G-Proteins

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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.