4IGU

Crystal structure of the RGS domain of CG5036

Summary for 4IGU

• Entry DOI: 10.2210/pdb4igu/pdb
• Descriptor: CG5036, CHLORIDE ION, SODIUM ION, ... (5 entities in total)
• Functional Keywords: regulator of g-protein signaling, gtpase-activating proteins (gap), regulator of gz-selective protein signaling 2, signaling protein
• Biological source: Drosophila melanogaster (Fruit fly)
• Total number of polymer chains: 2
• Total formula weight: 35381.09

Authors

Gabdulkhakov, A.,Tishchenko, S. (deposition date: 2012-12-18, release date: 2013-12-18, Last modification date: 2023-11-08)

Primary citation

Lin, C.,Koval, A.,Tishchenko, S.,Gabdulkhakov, A.,Tin, U.,Solis, G.P.,Katanaev, V.L.
Double suppression of the G alpha protein activity by RGS proteins
Mol.Cell, 53:663-671, 2014

PubMed Abstract: Regulator of G protein signaling (RGS) proteins accelerate GTP hydrolysis on G protein α subunits, restricting their activity downstream from G protein-coupled receptors. Here we identify Drosophila Double hit (Dhit) as a dual RGS regulator of Gαo. In addition to the conventional GTPase-activating action, Dhit possesses the guanine nucleotide dissociation inhibitor (GDI) activity, slowing the rate of GTP uptake by Gαo; both activities are mediated by the same RGS domain. These findings are recapitulated using homologous mammalian Gαo/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 Gαo mutant found in breast cancer escapes this GDI regulation. Our studies identify Dhit and its homologs as double-action regulators, inhibiting Gαo/i proteins both through suppression of their activation and acceleration of their inactivation through the single RGS domain.

PubMed: 24560274
DOI: 10.1016/j.molcel.2014.01.014

Experimental method

X-RAY DIFFRACTION (1.9 Å)