1zca

From Proteopedia

Revision as of 13:33, 20 March 2008

Crystal structure of G alpha 12 in complex with GDP, Mg2+ and AlF4-

Overview

The oncogenic G(12/13) subfamily of heterotrimeric G proteins transduces extracellular signals that regulate the actin cytoskeleton, cell cycle progression, and gene transcription. Previously, structural analyses of fully functional G alpha(12/13) subunits have been hindered by insufficient amounts of homogeneous, functional protein. Herein, we report that substitution of the N-terminal helix of G alpha(i1) for the corresponding region of G alpha12 or G alpha13 generated soluble chimeric subunits (G alpha(i/12) and G alpha(i/13)) that could be purified in sufficient amounts for crystallographic studies. Each chimera bound guanine nucleotides, G betagamma subunits, and effector proteins and exhibited GAP responses to p115RhoGEF and leukemia-associated RhoGEF. Like their wild-type counterparts, G alpha(i/13), but not G alpha(i/12), stimulated the activity of p115RhoGEF. Crystal structures of the G alpha(i/12) x GDP x AlF4(-) and G alpha(i/13) x GDP complexes were determined using diffraction data extending to 2.9 and 2.0 A, respectively. These structures reveal not only the native structural features of G alpha12 and G alpha13 subunits, which are expected to be important for their interactions with GPCRs and effectors such as G alpha-regulated RhoGEFs, but also novel conformational changes that are likely coupled to GTP hydrolysis in the G alpha(12/13) class of heterotrimeric G proteins.

About this Structure

1ZCA is a Single protein structure of sequence from Mus musculus. Full crystallographic information is available from OCA.

Reference

A new approach to producing functional G alpha subunits yields the activated and deactivated structures of G alpha(12/13) proteins., Kreutz B, Yau DM, Nance MR, Tanabe S, Tesmer JJ, Kozasa T, Biochemistry. 2006 Jan 10;45(1):167-74. PMID:16388592

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