4igu

Crystal structure of the RGS domain of CG5036

spinqualitylabelsall models 4igu, resolution 1.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4igu is a 2 chain structure with sequence from Drosophila melanogaster. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.9Å Ligands: CL, EDO, NA Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q8T017_DROME Publication Abstract from PubMed Regulator of G protein signaling (RGS) proteins accelerate GTP hydrolysis on G protein alpha subunits, restricting their activity downstream from G protein-coupled receptors. Here we identify Drosophila Double hit (Dhit) as a dual RGS regulator of Galphao. In addition to the conventional GTPase-activating action, Dhit possesses the guanine nucleotide dissociation inhibitor (GDI) activity, slowing the rate of GTP uptake by Galphao; both activities are mediated by the same RGS domain. These findings are recapitulated using homologous mammalian Galphao/i proteins and RGS19. Crystal structure and mutagenesis studies provide clues into the molecular mechanism for this unprecedented GDI activity. Physiologically, we confirm this activity in Drosophila asymmetric cell divisions and HEK293T cells. We show that the oncogenic Galphao mutant found in breast cancer escapes this GDI regulation. Our studies identify Dhit and its homologs as double-action regulators, inhibiting Galphao/i proteins both through suppression of their activation and acceleration of their inactivation through the single RGS domain. Double suppression of the Galpha protein activity by RGS proteins.,Lin C, Koval A, Tishchenko S, Gabdulkhakov A, Tin U, Solis GP, Katanaev VL Mol Cell. 2014 Feb 20;53(4):663-71. doi: 10.1016/j.molcel.2014.01.014. PMID:24560274 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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