4EKC

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

4EKC の概要

• エントリーDOI: 10.2210/pdb4ekc/pdb
• 関連するPDBエントリー: 1AGR 2AF0 2BCJ 2V4Z 4EKD
• 分子名称: Guanine nucleotide-binding protein G(q) subunit alpha, Regulator of G-protein signaling 2, GUANOSINE-5'-DIPHOSPHATE, ... (6 entities in total)
• 機能のキーワード: gtp-binding protein fold, regulator, g protein signaling, rgs, homology domain, gtpase activation, signaling protein-inhibitor complex, signaling protein/inhibitor
• 由来する生物種: Mus musculus (mouse); 詳細
• 細胞内の位置: Nucleus: P21279; Isoform 1: Cell membrane. Isoform 2: Cell membrane. Isoform 3: Cell membrane. Isoform 4: Cell membrane: P41220
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 114152.97

構造登録者

Tesmer, J.J.G.,Nance, M.R. (登録日: 2012-04-09, 公開日: 2013-01-30, 最終更新日: 2023-09-13)

主引用文献

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

実験手法

X-RAY DIFFRACTION (7.4 Å)