Structural Basis of G Protein-coupled Receptor-G Protein Interactions

Overview

Journal Nat Chem Biol

Specialties Biochemistry
Biology
Chemistry

Date 2010 Jun 1

PMID 20512139

Citations 42

Authors

Jianxin Hu

Yan Wang

Xiaohong Zhang

John R Lloyd

Jian Hua Li

Joel Karpiak

Stefano Costanzi

Jurgen Wess

Affiliations

Soon will be listed here.

Abstract

The interaction of G protein-coupled receptors (GPCRs) with heterotrimeric G proteins represents one of the most fundamental biological processes. However, the molecular architecture of the GPCR-G protein complex remains poorly defined. In the present study, we applied a comprehensive GPCR-G protein alpha subunit (Galpha) chemical cross-linking strategy to map a receptor-Galpha interface, both before and after agonist-induced receptor activation. Using the M(3) muscarinic acetylcholine receptor (M3R)-Galpha(q) system as a model system, we examined the ability of approximately 250 combinations of cysteine-substituted M3R and Galpha(q) proteins to undergo cross-link formation. We identified many specific M3R-Galpha(q) contact sites, in both the inactive and active receptor conformations, allowing us to draw conclusions regarding the basic architecture of the M3R-Galpha(q) interface and the nature of the conformational changes following receptor activation. As heterotrimeric G proteins as well as most GPCRs share a high degree of structural homology, our findings should be of broad general relevance.

Citing Articles

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