3CX6

Crystal Structure of PDZRhoGEF rgRGS Domain in a Complex with Galpha-13 Bound to GDP

Summary for 3CX6

• Entry DOI: 10.2210/pdb3cx6/pdb
• Related: 1SHZ 3CX7 3CX8
• Descriptor: Guanine nucleotide-binding protein alpha-13 subunit, Rho guanine nucleotide exchange factor 11, MAGNESIUM ION, ... (5 entities in total)
• Functional Keywords: signal transduction, protein complex, gtp-binding, lipoprotein, membrane, nucleotide-binding, palmitate, phosphoprotein, transducer, coiled coil, cytoplasm, gtpase activation, guanine-nucleotide releasing factor, signaling protein
• Biological source: Mus musculus (Mouse); More
• Cellular location: Membrane; Lipid-anchor: P27601; Cytoplasm (By similarity): Q9ES67
• Total number of polymer chains: 2
• Total formula weight: 63519.40

Authors

Sprang, S.R.,Chen, Z. (deposition date: 2008-04-23, release date: 2008-10-28, Last modification date: 2023-08-30)

Primary citation

Chen, Z.,Singer, W.D.,Danesh, S.M.,Sternweis, P.C.,Sprang, S.R.
Recognition of the Activated States of Galpha13 by the rgRGS Domain of PDZRhoGEF.
Structure, 16:1532-1543, 2008

PubMed Abstract: G12 class heterotrimeric G proteins stimulate RhoA activation by RGS-RhoGEFs. However, p115RhoGEF is a GTPase Activating Protein (GAP) toward Galpha13, whereas PDZRhoGEF is not. We have characterized the interaction between the PDZRhoGEF rgRGS domain (PRG-rgRGS) and the alpha subunit of G13 and have determined crystal structures of their complexes in both the inactive state bound to GDP and the active states bound to GDP*AlF (transition state) and GTPgammaS (Michaelis complex). PRG-rgRGS interacts extensively with the helical domain and the effector-binding sites on Galpha13 through contacts that are largely conserved in all three nucleotide-bound states, although PRG-rgRGS has highest affinity to the Michaelis complex. An acidic motif in the N terminus of PRG-rgRGS occupies the GAP binding site of Galpha13 and is flexible in the GDP*AlF complex but well ordered in the GTPgammaS complex. Replacement of key residues in this motif with their counterparts in p115RhoGEF confers GAP activity.

PubMed: 18940608
DOI: 10.1016/j.str.2008.07.009

Experimental method

X-RAY DIFFRACTION (2.5 Å)