Random-coil behavior and the dimensions of chemically unfolded proteins
Top Cited Papers
- 16 August 2004
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 101 (34), 12491-12496
- https://doi.org/10.1073/pnas.0403643101
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.Keywords
This publication has 57 references indexed in Scilit:
- Early Collapse is not an Obligate Step in Protein FoldingJournal of Molecular Biology, 2004
- Native-like Mean Structure in the Unfolded Ensemble of Small ProteinsJournal of Molecular Biology, 2002
- Biophysical Properties of the Synucleins and Their Propensities to FibrillateJournal of Biological Chemistry, 2002
- Distribution of molecular size within an unfolded state ensemble using small-angle X-ray scattering and pulse field gradient NMR techniquesJournal of Molecular Biology, 2002
- Equilibrium Collapse and the Kinetic ‘Foldability' of ProteinsBiochemistry, 2001
- NMR Spectroscopic Investigation of ψ Torsion Angle Distribution in Unfolded Ubiquitin from Analysis of 3J(Cα,Cα) Coupling Constants and Cross-Correlated Relaxation RatesJournal of the American Chemical Society, 2000
- Stabilisation of α-helices by site-directed mutagenesis reveals the importance of secondary structure in the transition state for acylphosphatase foldingJournal of Molecular Biology, 2000
- Folding kinetics of the SH3 domain of PI3 kinase by real-time NMR combined with optical spectroscopyJournal of Molecular Biology, 1998
- Protein Globularization During Folding. A Study by Synchrotron Small-angle X-ray ScatteringJournal of Molecular Biology, 1996
- Design of a heme-binding four-helix bundleJournal of the American Chemical Society, 1994