3AB3

Crystal structure of p115RhoGEF RGS domain in complex with G alpha 13

Summary for 3AB3

• Entry DOI: 10.2210/pdb3ab3/pdb
• Related: 1ZCB
• Descriptor: Guanine nucleotide-binding protein G(k) subunit alpha, Guanine nucleotide-binding protein subunit alpha-13, Rho guanine nucleotide exchange factor 1, MAGNESIUM ION, ... (6 entities in total)
• Functional Keywords: signal transduction, protein complex, gtp-binding, membrane, transducer, lipoprotein, nucleotide-binding, palmitate, phosphoprotein, gtpase activation, guanine-nucleotide releasing factor, signaling protein-membrane protein complex, signaling protein/membrane protein
• Biological source: Mus musculus (mouse); More
• Cellular location: Membrane ; Lipid-anchor : P27601; Cytoplasm : Q92888
• Total number of polymer chains: 4
• Total formula weight: 141164.68

Authors

Kukimoto-Niino, M.,Mishima, C.,Shirouzu, M.,Kozasa, T.,Yokoyama, S. (deposition date: 2009-11-30, release date: 2010-12-29, Last modification date: 2023-11-01)

Primary citation

Hajicek, N.,Kukimoto-Niino, M.,Mishima-Tsumagari, C.,Chow, C.R.,Shirouzu, M.,Terada, T.,Patel, M.,Yokoyama, S.,Kozasa, T.
Identification of critical residues in G(alpha)13 for stimulation of p115RhoGEF activity and the structure of the G(alpha)13-p115RhoGEF regulator of G protein signaling homology (RH) domain complex.
J.Biol.Chem., 286:20625-20636, 2011

PubMed Abstract: RH-RhoGEFs are a family of guanine nucleotide exchange factors that contain a regulator of G protein signaling homology (RH) domain. The heterotrimeric G protein Gα(13) stimulates the guanine nucleotide exchange factor (GEF) activity of RH-RhoGEFs, leading to activation of RhoA. The mechanism by which Gα(13) stimulates the GEF activity of RH-RhoGEFs, such as p115RhoGEF, has not yet been fully elucidated. Here, specific residues in Gα(13) that mediate activation of p115RhoGEF are identified. Mutation of these residues significantly impairs binding of Gα(13) to p115RhoGEF as well as stimulation of GEF activity. These data suggest that the exchange activity of p115RhoGEF is stimulated allosterically by Gα(13) and not through its interaction with a secondary binding site. A crystal structure of Gα(13) bound to the RH domain of p115RhoGEF is also presented, which differs from a previously crystallized complex with a Gα(13)-Gα(i1) chimera. Taken together, these data provide new insight into the mechanism by which p115RhoGEF is activated by Gα(13).

PubMed: 21507947
DOI: 10.1074/jbc.M110.201392

Experimental method

X-RAY DIFFRACTION (2.4 Å)