Premium
Urea denatured state ensembles contain extensive secondary structure that is increased in hydrophobic proteins
Author(s) -
Nick Pace C.,
HuyghuesDespointes Beatrice M. P.,
Fu Hailong,
Takano Kazufumi,
Scholtz J. Martin,
Grimsley Gerald R.
Publication year - 2010
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1002/pro.370
Subject(s) - chemistry , urea , protein secondary structure , denaturation (fissile materials) , polyproline helix , native state , protein structure , protein folding , intrinsically disordered proteins , crystallography , biophysics , biochemistry , peptide , biology , nuclear chemistry
The goal of this article is to gain a better understanding of the denatured state ensemble (DSE) of proteins through an experimental and computational study of their denaturation by urea. Proteins unfold to different extents in urea and the most hydrophobic proteins have the most compact DSE and contain almost as much secondary structure as folded proteins. Proteins that unfold to the greatest extent near pH 7 still contain substantial amounts of secondary structure. At low pH, the DSE expands due to charge–charge interactions and when the net charge per residue is high, most of the secondary structure is disrupted. The proteins in the DSE appear to contain substantial amounts of polyproline II conformation at high urea concentrations. In all cases considered, including staph nuclease, the extent of unfolding by urea can be accounted for using the data and approach developed in the laboratory of Wayne Bolen (Auton et al. , Proc Natl Acad Sci 2007; 104:15317–15323).