2V4Z

The crystal structure of the human G-protein subunit alpha (GNAI3) in complex with an engineered regulator of G-protein signaling type 2 domain (RGS2)

2V4Z の概要

• エントリーDOI: 10.2210/pdb2v4z/pdb
• 関連するPDBエントリー: 2AF0 2IHB
• 分子名称: GUANINE NUCLEOTIDE-BINDING PROTEIN G(K) SUBUNIT ALPHA, REGULATOR OF G-PROTEIN SIGNALING 2, GUANOSINE-5'-DIPHOSPHATE, ... (6 entities in total)
• 機能のキーワード: gtp hydrolysis, adp-ribosylation, nucleotide-binding, lipoprotein, gtp-binding, phosphoprotein, signal transduction inhibitor, guanine nucleotide binding protein, transmembrane signaling, g-protein coupled receptor, palmitate, myristate, transducer, cell cycle
• 由来する生物種: HOMO SAPIENS (HUMAN); 詳細
• 細胞内の位置: 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: 2
• 化学式量合計: 57193.59

構造登録者

Roos, A.K.,Soundararajan, M.,Pike, A.C.W.,Arrowsmith, C.H.,Weigelt, J.,Edwards, A.,Bountra, C.,Knapp, S. (登録日: 2008-09-30, 公開日: 2008-11-04, 最終更新日: 2023-12-13)

主引用文献

Kimple, A.J.,Soundararajan, M.,Hutsell, S.Q.,Roos, A.K.,Urban, D.J.,Setola, V.,Temple, B.R.,Roth, B.L.,Knapp, S.,Willard, F.S.,Siderovski, D.P.
Structural Determinants of G-Protein Alpha Subunit Selectivity by Regulator of G-Protein Signaling 2(Rgs2).
J.Biol.Chem., 284:19402-, 2009

PubMed Abstract: "Regulator of G-protein signaling" (RGS) proteins facilitate the termination of G protein-coupled receptor (GPCR) signaling via their ability to increase the intrinsic GTP hydrolysis rate of Galpha subunits (known as GTPase-accelerating protein or "GAP" activity). RGS2 is unique in its in vitro potency and selectivity as a GAP for Galpha(q) subunits. As many vasoconstrictive hormones signal via G(q) heterotrimer-coupled receptors, it is perhaps not surprising that RGS2-deficient mice exhibit constitutive hypertension. However, to date the particular structural features within RGS2 determining its selectivity for Galpha(q) over Galpha(i/o) substrates have not been completely characterized. Here, we examine a trio of point mutations to RGS2 that elicits Galpha(i)-directed binding and GAP activities without perturbing its association with Galpha(q). Using x-ray crystallography, we determined a model of the triple mutant RGS2 in complex with a transition state mimetic form of Galpha(i) at 2.8-A resolution. Structural comparison with unliganded, wild type RGS2 and of other RGS domain/Galpha complexes highlighted the roles of these residues in wild type RGS2 that weaken Galpha(i) subunit association. Moreover, these three amino acids are seen to be evolutionarily conserved among organisms with modern cardiovascular systems, suggesting that RGS2 arose from the R4-subfamily of RGS proteins to have specialized activity as a potent and selective Galpha(q) GAP that modulates cardiovascular function.

PubMed: 19478087
DOI: 10.1074/JBC.M109.024711

実験手法

X-RAY DIFFRACTION (2.8 Å)