3ab3
Crystal structure of p115RhoGEF RGS domain in complex with G alpha 13
Structural highlights
FunctionGNAI3_MOUSE Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems. G(k) is the stimulatory G protein of receptor-regulated K(+) channels. The active GTP-bound form prevents the association of RGS14 with centrosomes and is required for the translocation of RGS14 from the cytoplasm to the plasma membrane. May play a role in cell division. Publication Abstract from PubMedRH-RhoGEFs are a family of guanine nucleotide exchange factors that contain a regulator of G protein signaling homology (RH) domain. The heterotrimeric G protein Galpha(13) stimulates the guanine nucleotide exchange factor (GEF) activity of RH-RhoGEFs, leading to activation of RhoA. The mechanism by which Galpha(13) stimulates the GEF activity of RH-RhoGEFs, such as p115RhoGEF, has not yet been fully elucidated. Here, specific residues in Galpha(13) that mediate activation of p115RhoGEF are identified. Mutation of these residues significantly impairs binding of Galpha(13) to p115RhoGEF as well as stimulation of GEF activity. These data suggest that the exchange activity of p115RhoGEF is stimulated allosterically by Galpha(13) and not through its interaction with a secondary binding site. A crystal structure of Galpha(13) bound to the RH domain of p115RhoGEF is also presented, which differs from a previously crystallized complex with a Galpha(13)-Galpha(i1) chimera. Taken together, these data provide new insight into the mechanism by which p115RhoGEF is activated by Galpha(13). 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.,Hajicek N, Kukimoto-Niino M, Mishima-Tsumagari C, Chow CR, Shirouzu M, Terada T, Patel M, Yokoyama S, Kozasa T J Biol Chem. 2011 Jun 10;286(23):20625-36. Epub 2011 Apr 20. PMID:21507947[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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