Random-coil behavior and the dimensions of chemically unfolded proteins

Jonathan E. Kohn, Ian S. Millett, Jaby Jacob, Bojan Zagrovic, Thomas M. Dillon, Nikolina Cingel, Robin S. Dothager, Soenke Seifert, P. Thiyagarajan, Tobin R. Sosnick, M. Zahid Hasan, Vijay S. Pande, Ingo Ruczinski, Sebastian Doniach, Kevin W. Plaxco

Research output: Contribution to journalArticle

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 (RG) 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 RG of the remaining 26 polypeptides, which range from 16 to 549 residues, are well fitted (r2 = 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.

Original languageEnglish (US)
Pages (from-to)12491-12496
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume101
Issue number34
DOIs
StatePublished - Aug 24 2004

Fingerprint

Protein Unfolding
Peptides
Proteins
Hydrodynamics
Viscosity
Polymers
X-Rays

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Kohn, J. E., Millett, I. S., Jacob, J., Zagrovic, B., Dillon, T. M., Cingel, N., ... Plaxco, K. W. (2004). Random-coil behavior and the dimensions of chemically unfolded proteins. Proceedings of the National Academy of Sciences of the United States of America, 101(34), 12491-12496. https://doi.org/10.1073/pnas.0403643101

Random-coil behavior and the dimensions of chemically unfolded proteins. / Kohn, Jonathan E.; 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.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 101, No. 34, 24.08.2004, p. 12491-12496.

Research output: Contribution to journalArticle

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 2004, '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, pp. 12491-12496. https://doi.org/10.1073/pnas.0403643101
Kohn, Jonathan E. ; 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. / Random-coil behavior and the dimensions of chemically unfolded proteins. In: Proceedings of the National Academy of Sciences of the United States of America. 2004 ; Vol. 101, No. 34. pp. 12491-12496.
@article{f999c2762d1c443d817e9f0edbd1cd21,
title = "Random-coil behavior and the dimensions of chemically unfolded proteins",
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 (RG) 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 RG of the remaining 26 polypeptides, which range from 16 to 549 residues, are well fitted (r2 = 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.",
author = "Kohn, {Jonathan E.} and Millett, {Ian S.} and Jaby Jacob and Bojan Zagrovic and Dillon, {Thomas M.} and Nikolina Cingel and Dothager, {Robin S.} and Soenke Seifert and P. Thiyagarajan and Sosnick, {Tobin R.} and Hasan, {M. Zahid} and Pande, {Vijay S.} and Ingo Ruczinski and Sebastian Doniach and Plaxco, {Kevin W.}",
year = "2004",
month = "8",
day = "24",
doi = "10.1073/pnas.0403643101",
language = "English (US)",
volume = "101",
pages = "12491--12496",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "34",

}

TY - JOUR

T1 - Random-coil behavior and the dimensions of chemically unfolded proteins

AU - Kohn, Jonathan E.

AU - Millett, Ian S.

AU - Jacob, Jaby

AU - Zagrovic, Bojan

AU - Dillon, Thomas M.

AU - Cingel, Nikolina

AU - Dothager, Robin S.

AU - Seifert, Soenke

AU - Thiyagarajan, P.

AU - Sosnick, Tobin R.

AU - Hasan, M. Zahid

AU - Pande, Vijay S.

AU - Ruczinski, Ingo

AU - Doniach, Sebastian

AU - Plaxco, Kevin W.

PY - 2004/8/24

Y1 - 2004/8/24

N2 - 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 (RG) 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 RG of the remaining 26 polypeptides, which range from 16 to 549 residues, are well fitted (r2 = 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.

AB - 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 (RG) 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 RG of the remaining 26 polypeptides, which range from 16 to 549 residues, are well fitted (r2 = 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.

UR - http://www.scopus.com/inward/record.url?scp=4344716256&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=4344716256&partnerID=8YFLogxK

U2 - 10.1073/pnas.0403643101

DO - 10.1073/pnas.0403643101

M3 - Article

C2 - 15314214

AN - SCOPUS:4344716256

VL - 101

SP - 12491

EP - 12496

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 34

ER -