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PMID: 19212142 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review

Structural determinants involved in the formation and activation of G protein betagamma dimers.

Neuro-Signals ·Vol. 17 ·No. 1 ·2009-00-00 ·Pages 82-99

McIntire WE

Abstract

Heterotrimeric G proteins, composed of an alpha, beta and gamma subunit, represent one of the most important and dynamic families of signaling proteins. As a testament to the significance of G protein signaling, the hundreds of seven-transmembrane-spanning receptors that interact with G proteins are estimated to occupy 1-2% of the human genome. This broad diversity of receptors is echoed in the number of potential heterotrimer combinations that can arise from the 23 alpha subunit, 7 beta subunit and 12 gamma subunit isoforms that have been identified. The potential for such vast complexity implies that the receptor G protein interface is the site of much regulation. The historical model for the activation of a G protein holds that activated receptor catalyzes the exchange of GDP for GTP on the alpha subunit, inducing a conformational change that substantially lowers the affinity of alpha for betagamma. This decreased affinity enables dissociation of betagamma from alpha and receptor. The free form of betagamma is thought to activate effectors, until the hydrolysis of GTP by G alpha (aided by RGS proteins) allows the subunits to re-associate, effectively deactivating the G protein until another interaction with activated receptor.

MeSH Terms
Animals GTP-Binding Protein alpha Subunits/metabolism GTP-Binding Protein beta Subunits/chemistry,genetics,metabolism GTP-Binding Protein gamma Subunits/chemistry,genetics,metabolism Genetic Heterogeneity Humans Models, Molecular Protein Binding Protein Isoforms Protein Multimerization Protein Processing, Post-Translational Protein Stability Protein Structure, Quaternary Receptors, Adenosine A2/metabolism Receptors, Adrenergic, beta/metabolism Signal Transduction
Chemicals
GTP-Binding Protein alpha Subunits GTP-Binding Protein beta Subunits GTP-Binding Protein gamma Subunits Protein Isoforms Receptors, Adenosine A2 Receptors, Adrenergic, beta
Authors & Affiliations
1 authors, click to expand affiliations / ORCID
McIntire William E
Department of Pharmacology, University of Virginia Health System, Charlottesville, VA 22908, USA. wem2p@virginia.edu
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Article Info
Journal
Neuro-Signals
Abbr.
Neurosignals
ISSN
1424-8638
DOI
10.1159/000186692
Email
wem2p@virginia.edu
Published
2009-00-00
Epub
2009-00-12
Pages
82-99
Language
English
Region
Switzerland
NLM ID
101134359
PMCID
PMC2836951
Subset
IM
Grants
NIDDK NIH HHS · P30 DK067629 · United States
NIDDK NIH HHS · R01 DK019952 · United States
NIDDK NIH HHS · R01-DK-19952 · United States
External Links
PubMed source DOI: 10.1159/000186692 PMC Full Text
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