A simple thermodynamic test to discriminate between two-state and downhill folding

Journal of the American Chemical Society
Fabiana Y Oliva, Victor Muñoz

Abstract

The recent discovery of one-state folding, in which proteins unfold by progressive structural disorganizations (i.e., downhill folding), has emphasized the need for simple thermodynamic tests to discriminate between this behavior and classical two-state folding. On the basis of theoretical results from elementary statistical mechanical models, we propose such a test. The test involves monitoring the equilibrium unfolding transition induced by a combination of temperature and chemical denaturants with a probe that is sensitive to the average protein backbone conformation. The rationale is that the coupling between two different denaturation procedures can reveal subtle changes in protein conformational ensembles even when using bulk measurements. We demonstrate the applicability of the test by studying the unfolding process of the protein BBL, which has been previously characterized as a downhill folding protein. This test should be very useful for high-throughput design strategies and for the analysis of mutational effects in small proteins.

References

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Citations

Jan 11, 2008·European Biophysics Journal : EBJ·Ylva IvarssonStefano Gianni
Jul 13, 2006·Biochemistry·Athi N NaganathanVictor Muñoz
Aug 17, 2006·Journal of the American Chemical Society·Maxim S PometunA Joshua Wand
Apr 11, 2007·Journal of the American Chemical Society·Athi N NaganathanVictor Muñoz
Apr 10, 2010·Journal of the American Chemical Society·Patrick FarberAnthony Mittermaier
Aug 12, 2010·Journal of the American Chemical Society·Athi N NaganathanVictor Muñoz
May 5, 2012·Journal of the American Chemical Society·Michele CerminaraVictor Muñoz
Feb 15, 2008·Proceedings of the National Academy of Sciences of the United States of America·Wookyung YuIksoo Chang
Jan 2, 2009·Proceedings of the National Academy of Sciences of the United States of America·Peng LiVictor Muñoz
Dec 21, 2011·Proceedings of the National Academy of Sciences of the United States of America·Jianwei LiuVictor Muñoz
Aug 24, 2010·The Journal of Biological Chemistry·Tanay M DesaiVictor Muñoz
Oct 29, 2005·The Journal of Chemical Physics·Lidia PrietoAntonio Rey
Jun 15, 2007·The Journal of Chemical Physics·Pierpaolo BruscoliniMarco Zamparo
May 5, 2007·The Journal of Chemical Physics·Lidia Prieto, Antonio Rey
Nov 13, 2007·The Journal of Chemical Physics·Lidia Prieto, Antonio Rey
Dec 14, 2004·Proceedings of the National Academy of Sciences of the United States of America·Victor Muñoz, Jose M Sanchez-Ruiz
Jan 12, 2011·Annual Review of Physical Chemistry·Jose M Sanchez-Ruiz
Feb 5, 2016·Current Opinion in Structural Biology·Victor MuñozMourad Sadqi
Sep 15, 2010·Journal of Molecular Biology·Amrita Dasgupta, Jayant B Udgaonkar
Mar 8, 2016·Journal of Molecular Biology·C MillershipE R G Main
Dec 19, 2006·Journal of Molecular Biology·Diego U FerreiroElizabeth A Komives
Aug 30, 2005·Biophysical Journal·Maksim KouzaChin-Kun Hu
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Mar 29, 2016·Biophysical Chemistry·Stefano Gianni, Per Jemth
Nov 4, 2004·Journal of Molecular Biology·Neil FergusonAlan R Fersht
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Sep 20, 2005·Journal of Molecular Biology·Neil FergusonAlan R Fersht
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Jun 27, 2006·Nature·Mourad SadqiVictor Muñoz
Oct 15, 2005·Physical Biology·Huan-Xiang Zhou
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Nov 22, 2011·The Journal of Physical Chemistry. B·Mily Bhattacharya, Samrat Mukhopadhyay

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