PDBsum entry 4ekd

Signaling protein/inhibitor

PDB id: 4ekd

Contents

Protein chains

318 a.a.

132 a.a.

Ligands

GDP-ALF

MES

Metals

_MG

_CO ×2

_CL ×2

Waters ×16

PDB id:

4ekd

Name:

Signaling protein/inhibitor

Title:

Structure of human regulator of g protein signaling 2 (rgs2) in complex with murine galpha-q(r183c)

Structure:

Guanine nucleotide-binding protein g(q) subunit alpha. Chain: a. Fragment: unp residues 18-359. Synonym: guanine nucleotide-binding protein alpha-q. Engineered: yes. Mutation: yes. Regulator of g-protein signaling 2. Chain: b. Fragment: rgs domain, unp residues 72-203.

Source:

Mus musculus. Mouse. Organism_taxid: 10090. Gene: gnaq. Expressed in: trichoplusia ni. Expression_system_taxid: 7111. Homo sapiens. Human. Organism_taxid: 9606.

Resolution:

2.71Å R-factor: 0.193 R-free: 0.252

Authors:

J.J.G.Tesmer,M.R.Nance

Key ref:

M.R.Nance et al. (2013). Structural and functional analysis of the regulator of G protein signaling 2-gαq complex. Structure, 21, 438-448. PubMed id: 23434405 DOI: 10.1016/j.str.2012.12.016

Date:

09-Apr-12 Release date: 30-Jan-13

Protein chain

P21279  (GNAQ_MOUSE) -  Guanine nucleotide-binding protein G(q) subunit alpha from Mus musculus

Seq: 359 a.a.

Struc: 318 a.a.*

Protein chain

P41220  (RGS2_HUMAN) -  Regulator of G-protein signaling 2 from Homo sapiens

Seq: 211 a.a.

Struc: 132 a.a.*

* PDB and UniProt seqs differ at 8 residue positions (black crosses)

Enzyme reactions

• Enzyme class: Chain A: E.C.3.6.5.1 - heterotrimeric G-protein GTPase.
• Reaction: GTP + H2O = GDP + phosphate + H⁺

GTP + H2O = GDP (Bound ligand (Het Group name = GDP) corresponds exactly) + phosphate + H(+)

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1016/j.str.2012.12.016

Structure 21:438-448 (2013)

PubMed id: 23434405

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

M.R.Nance, B.Kreutz, V.M.Tesmer, R.Sterne-Marr, T.Kozasa, J.J.Tesmer.

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.