Dominant inhibitory mutations in the Mg super(2+)-binding site of Ras super(H) prevent its activation by GTP

We have previously demonstrated that substitution of Asn for Ser at position 17 of Ras super(H) yields a dominant inhibitory protein whose expression in cells interferes with endogenous Ras function. Subsequent structural studies have shown that the hydroxyl group of Ser-17 contributes to the bindin...

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Bibliographic Details
Published in:Molecular and cellular biology 1991-01, Vol.11 (10), p.4822-4829
Main Authors: Farnsworth, CL, Feig, LA
Format: Article
Language:English
Subjects:
GTP
magnesium
Ras
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Summary:We have previously demonstrated that substitution of Asn for Ser at position 17 of Ras super(H) yields a dominant inhibitory protein whose expression in cells interferes with endogenous Ras function. Subsequent structural studies have shown that the hydroxyl group of Ser-17 contributes to the binding of Mg super(2+) associated with bound nucleotide. Ih this report, we show that more subtle amino acid substitutions at this site that would be expected to interfere with complexing Mg super(2+), such as Cys or Ala, also generated dominant inhibitory mutants. A model is presented to explain how these properties could cause the mutant protein to inhibit the activation of endogenous Ras by competing for a guanine nucleotide-releasing factor.
ISSN:0270-7306