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

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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

All Science Journal Classification (ASJC) codes

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    Kohn, J. E., Millett, I. S., Jacob, J., Zagrovic, B., Dillon, T. M., Cingel, N., Dothager, R. S., Seifert, S., Thiyagarajan, P., Sosnick, T. R., Hasan, M. Z., Pande, V. S., Ruczinski, I., Doniach, S., & 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