Urea denatured state ensembles contain extensive secondary structure that is increased in hydrophobic proteins.


Abstract

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). Study holds ProTherm entries: 25662, 25663, 25664, 25665, 25666, 25667, 25668, 25669, 25670, 25671, 25672, 25673, 25674, 25675, 25676, 25677, 25678, 25679, 25680, 25681, 25682 Extra Details: urea denaturation; denatured state ensemble; m values; hydrophobic interactions; electrostatic interactions; polyproline II

Submission Details

ID: iM5iA8oB3

Submitter: Connie Wang

Submission Date: April 24, 2018, 8:55 p.m.

Version: 1

Publication Details
Nick Pace C;Huyghues-Despointes BM;Fu H;Takano K;Scholtz JM;Grimsley GR,Protein Sci. (2010) Urea denatured state ensembles contain extensive secondary structure that is increased in hydrophobic proteins. PMID:20198681
Additional Information

Structure view and single mutant data analysis

Study data

No weblogo for data of varying length.
Colors: D E R H K S T N Q A V I L M F Y W C G P
 

Data Distribution

Studies with similar sequences (approximate matches)

Correlation with other assays (exact sequence matches)


Relevant PDB Entries

Structure ID Release Date Resolution Structure Title
4CZ3 2015-02-18 HP24wt derived from the villin headpiece subdomain
2PPZ 2007-05-29 NMR solution Structure of the Villin Headpiece Mutant G34L
1QQV 1999-12-29 SOLUTION STRUCTURE OF THE HEADPIECE DOMAIN OF CHICKEN VILLIN
2JM0 2006-10-17 Solution structure of chicken villin headpiece subdomain containing a fluorinated side chain in the core
2VIK 1997-04-01 REFINED STRUCTURE OF THE ACTIN-SEVERING DOMAIN VILLIN 14T, DETERMINED BY SOLUTION NMR, MINIMIZED AVERAGE STRUCTURE
2VIL 1997-04-01 REFINED STRUCTURE OF THE ACTIN-SEVERING DOMAIN VILLIN 14T, DETERMINED BY SOLUTION NMR, 11 STRUCTURES
4CZ4 2015-02-18 HP24stab derived from the villin headpiece subdomain
1VII 1997-08-12 THERMOSTABLE SUBDOMAIN FROM CHICKEN VILLIN HEADPIECE, NMR, MINIMIZED AVERAGE STRUCTURE
1C54 2001-11-28 SOLUTION STRUCTURE OF RIBONUCLEASE SA
2LLF 2012-11-07 Sixth Gelsolin-like domain of villin in 5 mM CaCl2
1WY3 2005-05-03 0.95 Chicken villin subdomain HP-35, K65(NLE), N68H, pH7.0
1YRI 2005-05-03 1.0 Chicken villin subdomain HP-35, N68H, pH6.4
3TRV 2012-01-25 1.0 Crystal structure of quasiracemic villin headpiece subdomain containing (F5Phe17) substitution
1T2H 2004-12-21 1.0 Y81W mutant of RNase Sa from Streptomyces aureofaciens
1LNI 2002-07-31 1.0 CRYSTAL STRUCTURE ANALYSIS OF A RIBONUCLEASE FROM STREPTOMYCES AUREOFACIENS AT ATOMIC RESOLUTION (1.0 A)
2F4K 2006-04-11 1.05 Chicken villin subdomain HP-35, K65(NLE), N68H, K70(NLE), PH9
1YRF 2005-05-03 1.07 Chicken villin subdomain HP-35, N68H, pH6.7
1T2I 2004-12-21 1.1 T76W mutant of RNase Sa from Streptomyces aureofaciens
4GHO 2013-08-14 1.1 Crystal Structure Analysis of Streptomyces aureofaciens Ribonuclease S24A mutant
5I1S 2016-05-25 1.12 Villin headpiece subdomain with a Lys30 to APC substitution
1ZGX 2006-08-08 1.13 Crystal structure of ribonuclease mutant
1RGE 1996-10-14 1.15 HYDROLASE, GUANYLORIBONUCLEASE
1RGH 1996-10-14 1.2 HYDROLASE, GUANYLORIBONUCLEASE
1RGG 1996-10-14 1.2 HYDROLASE, GUANYLORIBONUCLEASE
1YNV 2005-07-19 1.2 Asp79 makes a large, unfavorable contribution to the stability of RNase Sa
1RGF 1996-10-14 1.2 HYDROLASE, GUANYLORIBONUCLEASE
4J5K 2014-05-28 1.23 Crystal structure analysis of Streptomyces aureofaciens ribonuclease Sa Y51F mutant
1I8V 2001-09-19 1.25 CRYSTAL STRUCTURE OF RNASE SA Y80F MUTANT
5I1N 2016-05-25 1.3 Villin headpiece subdomain with a Gln26 to beta-3-homoglutamine substitution
4J5G 2014-05-28 1.31 Crystal structure analysis of Streptomyces aureofaciens ribonuclease Sa T95A mutant
5I1O 2016-05-25 1.35 Villin headpiece subdomain with a Gln26 to ACPC substitution
1YU5 2005-09-06 1.4 Crystal Structure of the Headpiece Domain of Chicken Villin
5I1P 2016-05-25 1.4 Villin headpiece subdomain with a Lys30 to beta-3-homolysine substitution
2RJY 2008-09-23 1.4 Crystal structure of villin headpiece, P21 21 21 space group
1YU8 2005-09-06 1.45 Crystal Structure of the R37A Mutant of Villin Headpiece
2RJV 2008-09-23 1.45 Crystal structure of the H41Y mutant of villin headpiece, P 21 21 21 space group
3TJW 2012-01-25 1.46 Crystal Structure of Quasiracemic Villin Headpiece Subdomain Containing (F5Phe10) Substitution
1YU7 2005-09-06 1.5 Crystal Structure of the W64Y mutant of Villin Headpiece
2RJW 2009-02-17 1.55 The crystal structure of the H41Y mutant of villin headpiece, P61 SPACE GROUP.
1WY4 2005-05-03 1.55 Chicken villin subdomain HP-35, K65(NLE), N68H, pH5.1
3NKJ 2011-06-01 1.6 Crystal Structure of HP67 L61G
3A5E 2010-08-04 1.6 Crystal structure of 5K RNase Sa
1BOX 1999-12-29 1.6 N39S MUTANT OF RNASE SA FROM STREPTOMYCES AUREOFACIENS
3MYC 2011-11-02 1.7 Crystal Structure of HP67 H41F - P212121
1I70 2001-09-19 1.7 CRYSTAL STRUCTURE OF RNASE SA Y86F MUTANT
2RJX 2009-02-17 1.7 Crystal structure of the headpiece domain of chicken villin, P61 space group
1AY7 1999-03-02 1.7 RIBONUCLEASE SA COMPLEX WITH BARSTAR
1GMP 1993-10-31 1.7 COMPLEX OF RIBONUCLEASE FROM STREPTOMYCES AUREOFACIENS WITH 2'-GMP AT 1.7 ANGSTROMS RESOLUTION
1GMR 1993-10-31 1.77 COMPLEX OF RIBONUCLEASE FROM STREPTOMYCES AUREOFACIENS WITH 2'-GMP AT 1.7 ANGSTROMS RESOLUTION
1GMQ 1993-10-31 1.8 COMPLEX OF RIBONUCLEASE FROM STREPTOMYCES AUREOFACIENS WITH 2'-GMP AT 1.7 ANGSTROMS RESOLUTION
1UCI 2003-09-09 1.8 Mutants of RNase Sa
1UCK 2003-09-09 1.8 Mutants of RNase Sa
2SAR 1992-04-15 1.8 DETERMINATION AND RESTRAINED LEAST-SQUARES REFINEMENT OF THE CRYSTAL STRUCTURES OF RIBONUCLEASE SA AND ITS COMPLEX WITH 3'-GUANYLIC ACID AT 1.8 ANGSTROMS RESOLUTION
1SAR 1992-04-15 1.8 DETERMINATION AND RESTRAINED LEAST-SQUARES REFINEMENT OF THE CRYSTAL STRUCTURES OF RIBONUCLEASE SA AND ITS COMPLEX WITH 3'-GUANYLIC ACID AT 1.8 ANGSTROMS RESOLUTION
3MYE 2011-05-25 1.8 Crystal Structure of HP67 L61GL
1UCJ 2003-09-09 1.81 Mutants of RNase Sa
1UCL 2003-09-09 1.82 Mutants of RNase Sa
1RSN 1995-12-07 2.0 RIBONUCLEASE (RNASE SA) (E.C.3.1.4.8) COMPLEXED WITH EXO-2',3'-CYCLOPHOSPHOROTHIOATE
3TRW 2012-01-25 2.1 Crystal structure of racemic villin headpiece subdomain crystallized in space group P-1
3TRY 2012-01-25 2.3 Crystal structure of racemic villin headpiece subdomain in space group I-4c2
3MYA 2011-11-02 2.5 Crystal Structure of HP67 H41F - P61

Relevant UniProtKB Entries

Percent Identity Matching Chains Protein Accession Entry Name
100.0 Villin-1 P02640 VILI_CHICK
100.0 Guanyl-specific ribonuclease Sa P05798 RNSA_KITAU