Structure of the dominant negative S17N mutant of Ras.

Biochemistry
Nicolas NassarMiguel Garcia-Diaz

Abstract

The use of the dominant negative mutant of Ras has been crucial in elucidating the cellular signaling of Ras in response to the activation of various membrane-bound receptors. Although several point mutants of Ras exhibit a dominant negative effect, the asparagine to serine mutation at position 17 (S17N) remains the most popular and the most effective at inhibiting the activation of endogenous Ras. It is now widely accepted that the dominant negative effect is due to the ability of the mutant to sequester upstream activators and its inability to activate downstream effectors. Here, we present the crystal structure of RasS17N in the GDP-bound form. In the three molecules that populate the asymmetric unit, the Mg(2+) ion that normally coordinates the beta-phosphate is absent because of steric hindrance from the Asn17 side chain. Instead, a Ca(2+) ion is coordinating the alpha-phosphate. Also absent from one molecule is electron density for Phe28, a conserved residue that normally stabilizes the nucleotide's guanine base. Except for Phe28, the nucleotide makes conserved interactions with Ras. Combined, the inability of Phe28 to stabilize the guanine base and the absence of a Mg(2+) ion to neutralize the negative charges on the pho...Continue Reading

References

Oct 1, 1991·Molecular and Cellular Biology·C L Farnsworth, L A Feig
Apr 28, 1968·Journal of Molecular Biology·B W Matthews
Jun 1, 1994·Molecular and Cellular Biology·V JungD Broek
Jun 20, 1993·Journal of Molecular Biology·R A LaskowskiJ M Thornton
Mar 1, 1996·Biopolymers·M F SannerJ C Spehner
Aug 1, 1998·The Journal of Biological Chemistry·A B Vojtek, C J Der
Aug 5, 1998·Nature·P A Boriack-SjodinJ Kuriyan
Aug 24, 1999·Molecular and Cellular Biology·R H CoolA Wittinghofer
Nov 10, 2001·Science·I R Vetter, A Wittinghofer
Sep 6, 2002·Proceedings of the National Academy of Sciences of the United States of America·Brian E HallNicolas Nassar
Oct 24, 2002·Acta Crystallographica. Section D, Biological Crystallography·Paul D AdamsThomas C Terwilliger
Jan 2, 2003·Nature Reviews. Cancer·Julian Downward
Apr 26, 2003·Acta Crystallographica. Section A, Foundations of Crystallography·Zbyszek OtwinowskiWladek Minor
Jul 16, 2004·Molecular and Cellular Biology·Catherine HoganYasuyuki Fujita
Apr 28, 2005·Oncogene·Aurélien G DupuyJean de Gunzburg
May 10, 2005·The Journal of Biological Chemistry·Bradley FordNicolas Nassar
Mar 15, 2006·Structure·Bradley FordNicolas Nassar
Nov 4, 2009·Biochemistry·Bradley FordNicolas Nassar

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Citations

Jan 28, 2016·Chemical Reviews·Shaoyong LuJian Zhang
Jul 8, 2015·Proceedings of the National Academy of Sciences of the United States of America·Janyaporn PhuchareonOsamu Tetsu
Jul 17, 2015·Nature Communications·David WiegandtRoger S Goody
Sep 16, 2020·Physical Chemistry Chemical Physics : PCCP·Jianzhong ChenWeiliang Zhu
May 27, 2016·The Journal of Biological Chemistry·Zhenhao FangMitsuhiko Ikura
Jun 15, 2019·Nature Communications·Nicolas BeryTerence H Rabbitts
Aug 10, 2017·Biomolecules·Raffaele NicastroClaudio De Virgilio
Jun 11, 2020·American Journal of Physiology. Cell Physiology·Skylar FisherElizabeth Sztul
Aug 13, 2021·Proceedings of the National Academy of Sciences of the United States of America·Pau CastelFrank McCormick
Aug 5, 2021·Human Molecular Genetics·Masamune SakamotoNaomichi Matsumoto

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