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Science 12 December 1997:
Vol. 278. no. 5345, pp. 1943 - 1947
DOI: 10.1126/science.278.5345.1943
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Reports

Crystal Structure of the Adenylyl Cyclase Activator Gsalpha

Roger K. Sunahara, John J. G. Tesmer, Alfred G. Gilman, Stephen R. Sprang *

The crystal structure of Gsalpha , the heterotrimeric G protein alpha  subunit that stimulates adenylyl cyclase, was determined at 2.5 Å in a complex with guanosine 5'-O-(3-thiotriphosphate) (GTPgamma S). Gsalpha is the prototypic member of a family of GTP-binding proteins that regulate the activities of effectors in a hormone-dependent manner. Comparison of the structure of Gsalpha ·GTPgamma S with that of Gialpha ·GTPgamma S suggests that their effector specificity is primarily dictated by the shape of the binding surface formed by the switch II helix and the alpha 3-beta 5 loop, despite the high sequence homology of these elements. In contrast, sequence divergence explains the inability of regulators of G protein signaling to stimulate the GTPase activity of Gsalpha . The beta gamma binding surface of Gsalpha is largely conserved in sequence and structure to that of Gialpha , whereas differences in the surface formed by the carboxyl-terminal helix and the alpha 4-beta 6 loop may mediate receptor specificity.

R. K. Sunahara and A. G. Gilman, Department of Pharmacology, The University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75235-9041, USA.
J. J. G.Tesmer and S. R. Sprang, Howard Hughes Medical Institute and the Department of Biochemistry, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75235-9050, USA.
*   To whom correspondence should be addressed. E-mail: sprang{at}howie.swmed.edu

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