Structural highlights
Function[RGS16_MOUSE] Inhibits signal transduction by increasing the GTPase activity of G protein alpha subunits thereby driving them into their inactive GDP-bound form. Binds to G(i)-alpha and G(o)-alpha, but not to G(s)-alpha. Plays an important role in the phototransduction cascade by regulating the lifetime and effective concentration of activated transducin alpha. May regulate extra and intracellular mitogenic signals. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedHeterotrimeric G proteins relay extracellular cues from heptahelical transmembrane receptors to downstream effector molecules. Composed of an alpha subunit with intrinsic GTPase activity and a betagamma heterodimer, the trimeric complex dissociates upon receptor-mediated nucleotide exchange on the alpha subunit, enabling each component to engage downstream effector targets for either activation or inhibition as dictated in a particular pathway. To mitigate excessive effector engagement and concomitant signal transmission, the Galpha subunit's intrinsic activation timer (the rate of GTP hydrolysis) is regulated spatially and temporally by a class of GTPase accelerating proteins (GAPs) known as the regulator of G protein signaling (RGS) family. The array of G protein-coupled receptors, Galpha subunits, RGS proteins and downstream effectors in mammalian systems is vast. Understanding the molecular determinants of specificity is critical for a comprehensive mapping of the G protein system. Here, we present the 2.9 A crystal structure of the enigmatic, neuronal G protein Galpha(o) in the GTP hydrolytic transition state, complexed with RGS16. Comparison with the 1.89 A structure of apo-RGS16, also presented here, reveals plasticity upon Galpha(o) binding, the determinants for GAP activity, and the structurally unique features of Galpha(o) that likely distinguish it physiologically from other members of the larger Galpha(i) family, affording insight to receptor, GAP and effector specificity. Molecular architecture of Galphao and the structural basis for RGS16-mediated deactivation.,Slep KC, Kercher MA, Wieland T, Chen CK, Simon MI, Sigler PB Proc Natl Acad Sci U S A. 2008 Apr 29;105(17):6243-8. Epub 2008 Apr 23. PMID:18434540[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences | ||||||||||||||||||||
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