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- Title
Structural basis of G protein–coupled receptor–G protein interactions.
- Authors
Jianxin Hu; Yan Wang; Xiaohong Zhang; Lloyd, John R.; Jian Hua Li; Karpiak, Joel; Costanzi, Stefano; Wess, Jürgen
- 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 α subunit (Gα) chemical cross-linking strategy to map a receptor-Gα interface, both before and after agonist-induced receptor activation. Using the M3 muscarinic acetylcholine receptor (M3R)-Gαq system as a model system, we examined the ability of ~250 combinations of cysteine-substituted M3R and Gαq proteins to undergo cross-link formation. We identified many specific M3R-Gαq contact sites, in both the inactive and active receptor conformations, allowing us to draw conclusions regarding the basic architecture of the M3R-Gαq 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.
- Subjects
G proteins; ACETYLCHOLINE; COMBINATORICS; CHOLINERGIC mechanisms; CYSTEINE proteinases; HOMOLOGY (Biology)
- Publication
Nature Chemical Biology, 2010, Vol 6, Issue 7, p541
- ISSN
1552-4450
- Publication type
Article
- DOI
10.1038/nchembio.385