4EKD

Structure of human regulator of G protein signaling 2 (RGS2) in complex with murine Galpha-q(R183C)

Summary for 4EKD

• Entry DOI: 10.2210/pdb4ekd/pdb
• Related: 1AGR 2AF0 2BCJ 2V4Z 4EKC
• Descriptor: Guanine nucleotide-binding protein G(q) subunit alpha, Regulator of G-protein signaling 2, GUANOSINE-5'-DIPHOSPHATE, ... (9 entities in total)
• Functional Keywords: gtp-binding, regulator of g protein signaling, homology domain, gtpase activation, signaling protein-inhibitor complex, signaling protein/inhibitor
• Biological source: Mus musculus (mouse); More
• Total number of polymer chains: 2
• Total formula weight: 57460.50

Authors

Tesmer, J.J.G.,Nance, M.R. (deposition date: 2012-04-09, release date: 2013-01-30, Last modification date: 2023-09-13)

Primary citation

Nance, M.R.,Kreutz, B.,Tesmer, V.M.,Sterne-Marr, R.,Kozasa, T.,Tesmer, J.J.
Structural and functional analysis of the regulator of G protein signaling 2-g alpha q complex.
Structure, 21:438-448, 2013

PubMed Abstract: 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 RGS-Gαi/o complexes. Despite its unique pose, RGS2 maintains canonical interactions with the switch regions of Gαq in part because its α6 helix adopts a distinct conformation. We show that RGS2 forms extensive interactions with the α-helical domain of Gαq that contribute to binding affinity and GAP potency. RGS subfamilies that do not serve as GAPs for Gαq are unlikely to form analogous stabilizing interactions.

PubMed: 23434405
DOI: 10.1016/j.str.2012.12.016

Experimental method

X-RAY DIFFRACTION (2.71 Å)