title: Structure of Galphaq-p63RhoGEF-RhoA complex reveals a pathway for the activation of RhoA by GPCRs.
abstract: The guanine nucleotide exchange factor p63RhoGEF is an effector of the heterotrimeric guanine nucleotide-binding protein (G protein) Galphaq and thereby links Galphaq-coupled receptors (GPCRs) to the activation of the small-molecular-weight G protein RhoA. We determined the crystal structure of the Galphaq-p63RhoGEF-RhoA complex, detailing the interactions of Galphaq with the Dbl and pleckstrin homology (DH and PH) domains of p63RhoGEF. These interactions involve the effector-binding site and the C-terminal region of Galphaq and appear to relieve autoinhibition of the catalytic DH domain by the PH domain. Trio, Duet, and p63RhoGEF are shown to constitute a family of Galphaq effectors that appear to activate RhoA both in vitro and in intact cells. We propose that this structure represents the crux of an ancient signal transduction pathway that is expected to be important in an array of physiological processes.
authors: Institute of Experimental and Clinical Pharmacology and Toxicology, Medical Faculty Mannheim, University of Heidelberg, Maybachstrasse 14, D-68169 Mannheim, Germany.
authors: Susanne
authors: S
authors: Lutz
authors: Aruna
authors: A
authors: Shankaranarayanan
authors: Cassandra
authors: C
authors: Coco
authors: Marc
authors: M
authors: Ridilla
authors: Mark R
authors: MR
authors: Nance
authors: Christiane
authors: C
authors: Vettel
authors: Doris
authors: D
authors: Baltus
authors: Chris R
authors: CR
authors: Evelyn
authors: Richard R
authors: RR
authors: Neubig
authors: Thomas
authors: T
authors: Wieland
authors: John J G
authors: JJ
authors: Tesmer
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D002460:Cell Line; D018360:Crystallography, X-Ray; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000737:chemistry* / Q000378:metabolism; D020662:Guanine Nucleotide Exchange Factors / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D064067:Rho Guanine Nucleotide Exchange Factors; D015398:Signal Transduction; D020742:rhoA GTP-Binding Protein / Q000737:chemistry* / Q000378:metabolism
chemical_list: C475063:ARHGEF25 protein, human; D020662:Guanine Nucleotide Exchange Factors; D064067:Rho Guanine Nucleotide Exchange Factors; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D020742:rhoA GTP-Binding Protein