Crystal Structure of the Adenylyl Cyclase Activator G s α

Publisher Website
Google Scholar
Abstract
The crystal structure of Gs α, the heterotrimeric G protein α subunit that stimulates adenylyl cyclase, was determined at 2.5 Å in a complex with guanosine 5′-O-(3-thiotriphosphate) (GTPγS). Gs α 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 Gs α·GTPγS with that of Gi α·GTPγS suggests that their effector specificity is primarily dictated by the shape of the binding surface formed by the switch II helix and the α3-β5 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 Gs α. The βγ binding surface of Gs α is largely conserved in sequence and structure to that of Gi α, whereas differences in the surface formed by the carboxyl-terminal helix and the α4-β6 loop may mediate receptor specificity.