title: Structural and biochemical analysis of Ras-effector signaling via RalGDS.
abstract: The structure of the complex of Ras with the Ras-binding domain of its effector RalGDS (RGS-RBD), the first genuine Ras-effector complex, has been solved by X-ray crystallography. As with the Rap-RafRBD complex (Nasser et al., 1995), the interaction is via an inter-protein beta-sheet between the switch I region of Ras and the second strand of the RGS-RBD sheet, but the details of the interactions in the interface are remarkably different. Mutational studies were performed to investigate the contribution of selected interface residues to the binding affinity. Gel filtration experiments show that the Ras x RGS-RBD complex is a monomer. The results are compared to a recently determined structure of a similar complex using a Ras mutant (Huang et al., 1998) and are discussed in relation to partial loss-of-function mutations and the specificity of Ras versus Rap binding.
authors.affiliation: Max-Planck-Institut für molekulare Physiologie, Abteilung Strukturelle Biologie, Dortmund, Germany.
authors.forename: I R
authors.initials: IR
authors.lastname: Vetter
authors.forename: T
authors.initials: T
authors.lastname: Linnemann
authors.forename: S
authors.initials: S
authors.lastname: Wohlgemuth
authors.forename: M
authors.initials: M
authors.lastname: Geyer
authors.forename: H R
authors.initials: HR
authors.lastname: Kalbitzer
authors.forename: C
authors.initials: C
authors.lastname: Herrmann
authors.forename: A
authors.initials: A
authors.lastname: Wittinghofer
mesh_terms: D018360:Crystallography, X-Ray; D019204:GTP-Binding Proteins / Q000737:chemistry* / Q000502:physiology; D016336:Gene Products, vpr / Q000737:chemistry / Q000502:physiology; D008958:Models, Molecular; D016296:Mutagenesis; D011485:Protein Binding; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D015398:Signal Transduction; D020726:ral Guanine Nucleotide Exchange Factor; D020668:rap GTP-Binding Proteins; D018631:ras Proteins / Q000737:chemistry* / Q000502:physiology
chemical_list: D016336:Gene Products, vpr; D020726:ral Guanine Nucleotide Exchange Factor; D019204:GTP-Binding Proteins; D020668:rap GTP-Binding Proteins; D018631:ras Proteins