Evidence for distinct mechanisms of transition state stabilization of GTPases by fluoride

S Vincent, M Brouns, M J Hart, J Settleman

Research output: Contribution to JournalArticleAcademicpeer-review


GTPase-activating proteins (GAPs) function by stabilizing the GTPase transition state. This has been most clearly demonstrated by the formation of a high-affinity complex between various GAPs and GDP-bound GTPases in the presence of aluminum tetrafluoride, which can mimic the gamma-phosphate of GTP. Herein, we report that p190 RhoGAP forms a high-affinity complex with Rho GTPases in the presence of fluoride ions, suggesting that p190 also functions to stabilize the GTPase transition state. However, this Rho-p190 complex does not require aluminum ions or even guanine nucleotide, indicating a distinct role for fluoride that is not consistent with the gamma-phosphate-mimicking hypothesis. These results indicate that it is necessary to reconsider the assumed role of fluoride in stabilizing a variety of other GTPase-GAP interactions where the requirement for aluminum or guanine nucleotide has not yet been addressed.

Original languageEnglish
Pages (from-to)2210-2215
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number5
Publication statusPublished - 3 Mar 1998
Externally publishedYes


  • 3T3 Cells
  • Animals
  • COS Cells
  • Cell Line
  • Enzyme Stability
  • Fibroblasts
  • GTP Phosphohydrolases/biosynthesis
  • GTP-Binding Proteins/biosynthesis
  • GTPase-Activating Proteins
  • Glutathione Transferase/biosynthesis
  • Guanosine 5'-O-(3-Thiotriphosphate)/pharmacology
  • Guanosine Diphosphate/pharmacology
  • Humans
  • Kinetics
  • Mice
  • Protein Biosynthesis
  • Proteins/chemistry
  • Recombinant Fusion Proteins/biosynthesis
  • Sequence Deletion
  • Sodium Fluoride/pharmacology
  • Transfection


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