title: Perturbation of the conformational equilibria in Ras by selective mutations as studied by 31P NMR spectroscopy.
abstract: Ras regulates a variety of different signal transduction pathways acting as molecular switch. It was shown by liquid and solid-state (31)P NMR spectroscopy that Ras exists in the guanosine-5'-(beta,gamma-imido)triphosphate bound form in at least two conformational states interconverting in millisecond time scale. The relative population between the two conformational states affects drastically the affinity of Ras to its effectors. (31)P NMR spectroscopy shows that the conformational equilibrium can be shifted specifically by point mutations, including mutations with oncogenic potential, thus modifying the effector interactions and their coupling to dynamic properties of the protein.
authors.affiliation: Universität Regensburg, Institut für Biophysik und physikalische Biochemie, Universitätsstrasse 31, 93053 Regensburg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Spoerner
authors.forename: Alfred
authors.initials: A
authors.lastname: Wittinghofer
authors.forename: Hans Robert
authors.initials: HR
authors.lastname: Kalbitzer
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D004926:Escherichia coli / Q000235:genetics; D020690:GTPase-Activating Proteins / Q000378:metabolism; D011905:Genes, ras; D014644:Genetic Variation; D006153:Guanosine Diphosphate / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D010758:Phosphorus / Q000737:chemistry; D010759:Phosphorus Isotopes; D017354:Point Mutation; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D015398:Signal Transduction; D013696:Temperature; D013912:Threonine / Q000378:metabolism; D018631:ras Proteins / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism
chemical_list: D020690:GTPase-Activating Proteins; D010759:Phosphorus Isotopes; D006153:Guanosine Diphosphate; D010758:Phosphorus; D013912:Threonine; D018631:ras Proteins