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Structural and functional analysis of the regulator of G protein signaling 2-g?q complex.

ABSTRACT: The heterotrimeric G protein G?q is a key regulator of blood pressure, and excess G?q signaling leads to hypertension. A specific inhibitor of G?q is the GTPase activating protein (GAP) known as regulator of G protein signaling 2 (RGS2). The molecular basis for how G?q/11 subunits serve as substrates for RGS proteins and how RGS2 mandates its selectivity for G?q is poorly understood. In crystal structures of the RGS2-G?q complex, RGS2 docks to G?q in a different orientation from that observed in RGS-G?i/o complexes. Despite its unique pose, RGS2 maintains canonical interactions with the switch regions of G?q in part because its ?6 helix adopts a distinct conformation. We show that RGS2 forms extensive interactions with the ?-helical domain of G?q that contribute to binding affinity and GAP potency. RGS subfamilies that do not serve as GAPs for G?q are unlikely to form analogous stabilizing interactions.

SUBMITTER: Nance MR

PROVIDER: S-EPMC3638996 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature

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Structural and functional analysis of the regulator of G protein signaling 2-gαq complex.

Nance Mark R MR Kreutz Barry B Tesmer Valerie M VM Sterne-Marr Rachel R Kozasa Tohru T Tesmer John J G JJ

Structure (London, England : 1993) 20130221 3

The heterotrimeric G protein Gαq is a key regulator of blood pressure, and excess Gαq signaling leads to hypertension. A specific inhibitor of Gαq is the GTPase activating protein (GAP) known as regulator of G protein signaling 2 (RGS2). The molecular basis for how Gαq/11 subunits serve as substrates for RGS proteins and how RGS2 mandates its selectivity for Gαq is poorly understood. In crystal structures of the RGS2-Gαq complex, RGS2 docks to Gαq in a different orientation from that observed in ...[more]

PMID: 23434405

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