What is the role of the helical domain of Gsα in the GTPase reaction?

Tamar Shnerb, Naama Lin, Avital Shurki*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Structural analysis of Gsα shows that it is composed of two domains: the ras-like domain (RD) that is conserved in all members of the GTPase superfamily and is homologous to the monomelic G-proteins (e.g., p21 ras) and an α-helical domain (HD) that is unique to heterotrimeric G-proteins. Little is known about the function of the HD. Recent experiments by Bourne and co-workers, who expressed both the RD and the HD of Gsα separately and found that GTP hydrolysis is very slow if only recombinant RD is present but is accelerated when the HD is added, suggest that the HD serves as an intrinsic GTPase-activating protein (GAP). In this work, the GTP hydrolysis in Gsα was studied. The results obtained by calculating catalytic effects with and without the HD provide evidence for the role of the HD as a GAP. It is demonstrated that a major part of the catalysis is obtained because of an allosteric influence of the HD on the RD. Structural as well as energetic considerations suggest that the HD confines the RD to a more compact conformation, pushing the phosphate into an orientation where it is further stabilized, thus lowering the overall reaction barrier. The resemblance between the behavior of rasGAP and the HD suggests that the conclusion may be a general conclusion, applicable for all of the G-protein members.

Original languageAmerican English
Pages (from-to)10875-10885
Number of pages11
JournalBiochemistry
Volume46
Issue number38
DOIs
StatePublished - 25 Sep 2007

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