Issue 14, 2010
From the journal:

Physical Chemistry Chemical Physics

A natural missing link between activated and downhill protein folding scenarios†

Feng Liu,a   Caroline Maynard,b   Gregory Scott,c   Artem Melnykov,b   Kathleen B. Hall*b  and  Martin Gruebele*acd  

* Corresponding authors

a Center for Biophysics and Computational Biology, University of Illinois at Urbana-Champaign, USA
E-mail: gruebele@scs.uiuc.edu
Fax: (217) 244 3186
Tel: (217) 333 1624

b Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, USA
E-mail: kathleenhal@gmail.com
Fax: (314) 362 7183
Tel: (314) 362 4196

c Department of Chemistry, University of Illinois at Urbana-Champaign, USA

d Department of Physics, University of Illinois at Urbana-Champaign, USA

Abstract

We propose protein PTB1∶4W as a good candidate for engineering into a downhill folder. PTB1∶4W has a probe-dependent thermal unfolding curve and sub-millisecond T-jump relaxation kinetics on more than one time scale. Its refolding rate in denaturant is a non-linear function of denaturant concentration (curved chevron plot). Yet at high denaturant concentration its unfolding is probe-independent, and the folding kinetics can be fitted to a single exponential decay. The domain appears to fold via a mechanism between downhill folding and activated folding over several small barriers, and when denaturant is added, one of these barriers greatly increases and simplifies the observed folding to apparent two-state kinetics. We predict the simplest free energy function consistent with the thermal denaturation and kinetics experiments by using the singular value Smoluchowski dynamics (SVSD) model. PTB1∶4W is a natural ‘missing link’ between downhill and activated folding. We suggest mutations that could move the protein into the downhill folding limit.

Graphical abstract: A natural missing link between activated and downhill protein folding scenarios

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Article information

DOI
https://doi.org/10.1039/B925033F
Article type
Paper
Submitted
27 Nov 2009
Accepted
11 Jan 2010
First published
11 Feb 2010

Phys. Chem. Chem. Phys., 2010,12, 3542-3549

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A natural missing link between activated and downhill protein folding scenarios

F. Liu, C. Maynard, G. Scott, A. Melnykov, K. B. Hall and M. Gruebele, Phys. Chem. Chem. Phys., 2010, 12, 3542 DOI: 10.1039/B925033F

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