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PMID: 15314214 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

Random-coil behavior and the dimensions of chemically unfolded proteins.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 101 ·No. 34 ·2004-08-24 ·Pages 12491-6

Kohn JE, Millett IS, Jacob J, Zagrovic B, Dillon TM, Cingel N, Dothager RS, Seifert S, Thiyagarajan P, Sosnick TR, Hasan MZ, Pande VS, Ruczinski I, Doniach S, Plaxco KW

Abstract

Spectroscopic studies have identified a number of proteins that appear to retain significant residual structure under even strongly denaturing conditions. Intrinsic viscosity, hydrodynamic radii, and small-angle x-ray scattering studies, in contrast, indicate that the dimensions of most chemically denatured proteins scale with polypeptide length by means of the power-law relationship expected for random-coil behavior. Here we further explore this discrepancy by expanding the length range of characterized denatured-state radii of gyration (R(G)) and by reexamining proteins that reportedly do not fit the expected dimensional scaling. We find that only 2 of 28 crosslink-free, prosthetic-group-free, chemically denatured polypeptides deviate significantly from a power-law relationship with polymer length. The R(G) of the remaining 26 polypeptides, which range from 16 to 549 residues, are well fitted (r(2) = 0.988) by a power-law relationship with a best-fit exponent, 0.598 +/- 0.028, coinciding closely with the 0.588 predicted for an excluded volume random coil. Therefore, it appears that the mean dimensions of the large majority of chemically denatured proteins are effectively indistinguishable from the mean dimensions of a random-coil ensemble.

MeSH Terms
Guanidine/chemistry Humans Protein Denaturation Protein Folding Protein Structure, Secondary Proteins/chemistry Thermodynamics Urea/chemistry
Chemicals
Proteins Urea Guanidine
Authors & Affiliations
15 authors, click to expand affiliations / ORCID
Kohn Jonathan E
Interdepartmental Program in Biomolecular Science and Engineering, University of California-Santa Barbara, Santa Barbara, CA 93106, USA.
Millett Ian S
Jacob Jaby
Zagrovic Bojan
Dillon Thomas M
Cingel Nikolina
Dothager Robin S
Seifert Soenke
Thiyagarajan P
Sosnick Tobin R
Hasan M Zahid
Pande Vijay S
Ruczinski Ingo
Doniach Sebastian
Plaxco Kevin W
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.0403643101
Published
2004-08-24
Epub
2004-00-16
Pages
12491-6
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC515087
Subset
IM
Corrections
ErratumIn
-
External Links
PubMed source DOI: 10.1073/pnas.0403643101 PMC Full Text View journal details
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