Evidence for distinct mechanisms of transition state stabilization of GTPases by fluoride
AUTOR(ES)
Vincent, Sylvie
FONTE
The National Academy of Sciences
RESUMO
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.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=19296Documentos Relacionados
- Evolutionary specialization of a tryptophan indole group for transition-state stabilization by eukaryotic transglutaminases
- Evidence against stabilization of the transition state oxyanion by a pKa-perturbed RNA base in the peptidyl transferase center
- Physical evidence for distinct mechanisms of translational control by upstream open reading frames
- Transition-state stabilization in the mechanism of tyrosyl-tRNA synthetase revealed by protein engineering.
- Evidence for distinct signaling mechanisms in two mammalian olfactory sense organs.
