Structural determinants involved in the formation and activation of G protein betagamma dimers.
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.
McIntire
William E
WE
Department of Pharmacology, University of Virginia Health System, Charlottesville, VA 22908, USA. wem2p@virginia.edu
D000818:Animals; D044385:GTP-Binding Protein alpha Subunits / Q000378:metabolism; D044387:GTP-Binding Protein beta Subunits / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D044388:GTP-Binding Protein gamma Subunits / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018740:Genetic Heterogeneity; D006801:Humans; D008958:Models, Molecular; D011485:Protein Binding; D020033:Protein Isoforms; D055503:Protein Multimerization; D011499:Protein Processing, Post-Translational; D055550:Protein Stability; D020836:Protein Structure, Quaternary; D043683:Receptors, Adenosine A2 / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D015398:Signal Transduction
D044385:GTP-Binding Protein alpha Subunits; D044387:GTP-Binding Protein beta Subunits; D044388:GTP-Binding Protein gamma Subunits; D020033:Protein Isoforms; D043683:Receptors, Adenosine A2; D011943:Receptors, Adrenergic, beta