Formation of a transition-state analog of the Ras GTPase reaction by Ras-GDP, tetrafluoroaluminate, and GTPase-activating proteins.
Unlike the alpha subunits of heterotrimeric guanosine triphosphate (GTP)-binding proteins, Ras-related GTP-binding proteins have hitherto been considered not to bind or become activated by tetrafluoroaluminate (AIF4-). However, the product of the proto-oncogene ras in its guanosine diphosphate (GDP)-bound form interacted with AIF4 - in the presence of stoichiometric amounts of either of the guanosine triphosphatase (GTPase)-activating proteins (GAPs) p120GAP and neurofibromin. Neither oncogenic Ras nor a GAP mutant without catalytic activity produced such a complex. Together with the finding that the Ras-binding domain of the protein kinase c-Raf, whose binding site on Ras overlaps that of the GAPs, did not induce formation of such a complex, this result suggests that GAP and neurofibromin stabilize the transition state of the GTPase reaction of Ras.
Mittal
R
R
Abteilung Strukturelle Biologie, Max-Planck-Institut für Molekulare Physiologie, Dortmund, Germany.
Ahmadian
M R
MR
Goody
R S
RS
Wittinghofer
A
A
D017607:Aluminum Compounds / Q000378:metabolism*; D000595:Amino Acid Sequence; D005459:Fluorides / Q000378:metabolism*; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D020690:GTPase-Activating Proteins; D006153:Guanosine Diphosphate / Q000378:metabolism; D008969:Molecular Sequence Data; D016296:Mutagenesis; D025542:Neurofibromin 1; D011506:Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D013050:Spectrometry, Fluorescence; D020703:ras GTPase-Activating Proteins; D018631:ras Proteins / Q000378:metabolism*
D017607:Aluminum Compounds; D020690:GTPase-Activating Proteins; D025542:Neurofibromin 1; D011506:Proteins; D020703:ras GTPase-Activating Proteins; D006153:Guanosine Diphosphate; C050992:tetrafluoroaluminate; D020558:GTP Phosphohydrolases; D018631:ras Proteins; D005459:Fluorides