Ion-ion interactions in the denatured state contribute to the stabilization of CutA1 proteins

Scientific Reports
K YutaniYasumasa Joti

Abstract

In order to elucidate features of the denatured state ensembles that exist in equilibrium with the native state under physiological conditions, we performed 1.4-μs molecular dynamics (MD) simulations at 400 K and 450 K using the monomer subunits of three CutA1 mutants from Escherichia coli: an SH-free mutant (Ec0SH) with denaturation temperature (Td) = 85.6 °C, a hydrophobic mutant (Ec0VV) with Td = 113.3 °C, and an ionic mutant (Ec0VV_6) with Td = 136.8 °C. The occupancy of salt bridges by the six substituted charged residues in Ec0VV_6 was 140.1% at 300 K and 89.5% at 450 K, indicating that even in the denatured state, salt bridge occupancy was high, approximately 60% of that at 300 K. From these results, we can infer that proteins from hyperthermophiles with a high ratio of charged residues are stabilized by a decrease in conformational entropy due to ion-ion interactions in the denatured state. The mechanism must be comparable to the stabilization conferred by disulfide bonds within a protein. This suggests that introduction of charged residues, to promote formation of salt bridges in the denatured state, would be a simple way to rationally design stability-enhanced mutants.

References

Jan 1, 1968·Advances in Protein Chemistry·C Tanford
Mar 31, 1999·Proceedings of the National Academy of Sciences of the United States of America·P J HaneyG J Olsen
Aug 10, 2000·Protein Science : a Publication of the Protein Society·C N PaceK L Shaw
Nov 23, 2000·Proceedings of the National Academy of Sciences of the United States of America·U MayorA R Fersht
Mar 10, 2001·Microbiology and Molecular Biology Reviews : MMBR·C Vieille, G J Zeikus
Mar 16, 2001·Trends in Biotechnology·J M Sanchez-Ruiz, G I Makhatadze
Mar 21, 2001·Critical Reviews in Biochemistry and Molecular Biology·R Sterner, W Liebl
Sep 12, 2001·Trends in Biochemical Sciences·A Karshikoff, R Ladenstein
Feb 26, 2003·The Journal of Biological Chemistry·Karsten Suhre, Jean-Michel Claverie
Sep 25, 2003·Proceedings of the National Academy of Sciences of the United States of America·Srebrenka RobicSusan Marqusee
Feb 20, 2004·Journal of the American Chemical Society·Andrew S Thomas, Adrian H Elcock
Jun 7, 2005·Protein Science : a Publication of the Protein Society·Jared M TrefethenDavid N Brems
Oct 29, 2005·Biophysical Chemistry·M SadeghiB Ranjbar
Jan 11, 2007·The Journal of Chemical Physics·Giovanni BussiMichele Parrinello
Feb 3, 2007·Physical Chemistry Chemical Physics : PCCP·Jiayun Pang, Rudolf K Allemann
May 13, 2008·Journal of Molecular Biology·Marcus WallgrenMagnus Wolf-Watz
Mar 12, 2010·Journal of the American Chemical Society·Vincent A VoelzVijay S Pande
Jul 5, 2011·Biophysical Journal·Lucas Sawle, Kingshuk Ghosh
Oct 7, 2011·Chemical Society Reviews·Fabio Sterpone, Simone Melchionna
Feb 22, 2012·Journal of the American Chemical Society·Kresten Lindorff-LarsenDavid E Shaw
May 21, 2013·Current Opinion in Structural Biology·Hein J WijmaDick B Janssen
Oct 27, 2014·Journal of Biochemistry·Bagautdin BagautdinovKatsuhide Yutani
Mar 1, 2008·Journal of Chemical Theory and Computation·Berk HessErik Lindahl

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Methods Mentioned

BETA
Ec0SH

Software Mentioned

FoldX
GROMACS
QUANTA2000
LINCS
GROMOS

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