1ZCA

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

Summary for 1ZCA

• Entry DOI: 10.2210/pdb1zca/pdb
• Related: 1ZCB
• Descriptor: G alpha i/12, MAGNESIUM ION, TETRAFLUOROALUMINATE ION, ... (5 entities in total)
• Functional Keywords: gtp-binding, lipoprotein, membrane, palmitate, transducer, signaling protein
• Biological source: Mus musculus (house mouse); More
• Cellular location: Cell membrane ; Lipid-anchor : P27600
• Total number of polymer chains: 2
• Total formula weight: 85046.03

Authors

Nance, M.R.,Tesmer, J.J.G. (deposition date: 2005-04-11, release date: 2005-11-15, Last modification date: 2023-08-23)

Primary citation

Kreutz, B.,Yau, D.M.,Nance, M.R.,Tanabe, S.,Tesmer, J.J.,Kozasa, T.
A new approach to producing functional G alpha subunits yields the activated and deactivated structures of G alpha(12/13) proteins.
Biochemistry, 45:167-174, 2006

PubMed Abstract: 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.

PubMed: 16388592
DOI: 10.1021/bi051729t

Experimental method

X-RAY DIFFRACTION (2.9 Å)