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PMID: 22032986 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Review

Diversity and modularity of G protein-coupled receptor structures.

Trends in pharmacological sciences ·Vol. 33 ·No. 1 ·2012-01-00 ·Pages 17-27

Katritch V, Cherezov V, Stevens RC

Abstract

G protein-coupled receptors (GPCRs) comprise the most 'prolific' family of cell membrane proteins, which share a general mechanism of signal transduction, but greatly vary in ligand recognition and function. Crystal structures are now available for rhodopsin, adrenergic, and adenosine receptors in both inactive and activated forms, as well as for chemokine, dopamine, and histamine receptors in inactive conformations. Here we review common structural features, outline the scope of structural diversity of GPCRs at different levels of homology, and briefly discuss the impact of the structures on drug discovery. Given the current set of GPCR crystal structures, a distinct modularity is now being observed between the extracellular (ligand-binding) and intracellular (signaling) regions. The rapidly expanding repertoire of GPCR structures provides a solid framework for experimental and molecular modeling studies, and helps to chart a roadmap for comprehensive structural coverage of the whole superfamily and an understanding of GPCR biological and therapeutic mechanisms.

MeSH Terms
Animals Humans Ligands Protein Conformation Receptors, G-Protein-Coupled/chemistry
Chemicals
Ligands Receptors, G-Protein-Coupled
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Katritch Vsevolod
Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Cherezov Vadim
Stevens Raymond C
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Article Info
Journal
Trends in pharmacological sciences
Abbr.
Trends Pharmacol Sci
ISSN
1873-3735
DOI
10.1016/j.tips.2011.09.003
Published
2012-01-00
Epub
2011-00-25
Pages
17-27
Language
English
Region
England
NLM ID
7906158
PMCID
PMC3259144
Subset
IM
Grants
NIGMS NIH HHS · U54 GM094618-02 · United States
NIGMS NIH HHS · P50 GM073197-07 · United States
NIGMS NIH HHS · P50 GM073197-08 · United States
NIGMS NIH HHS · U54 GM094618-01 · United States
NIGMS NIH HHS · P50 GM073197 · United States
NIGMS NIH HHS · U54 GM094618 · United States
External Links
PubMed source DOI: 10.1016/j.tips.2011.09.003 PMC Full Text View journal details
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