1zca

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spinqualitylabelsall models 1zca, resolution 2.9Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

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 with MG, ALF and GDP as ligands. 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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