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

Sylvie Vincent, Madeleine Brouns, Matthew J. Hart, Jeffrey Settleman

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23 Scopus citations

Abstract

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 γ-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 γ-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 (US)
Pages (from-to)2210-2215
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume95
Issue number5
DOIs
StatePublished - Mar 3 1998

ASJC Scopus subject areas

  • General

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