Random-coil behavior and the dimensions of chemically unfolded proteins.
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.
Interdepartmental Program in Biomolecular Science and Engineering, University of California-Santa Barbara, Santa Barbara, CA 93106, USA.
Jonathan E
JE
Kohn
Ian S
IS
Millett
Jaby
J
Jacob
Bojan
B
Zagrovic
Thomas M
TM
Dillon
Nikolina
N
Cingel
Robin S
RS
Dothager
Soenke
S
Seifert
P
P
Thiyagarajan
Tobin R
TR
Sosnick
M Zahid
MZ
Hasan
Vijay S
VS
Pande
Ingo
I
Ruczinski
Sebastian
S
Doniach
Kevin W
KW
Plaxco
D019791:Guanidine / Q000737:chemistry; D006801:Humans; D011489:Protein Denaturation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry*; D013816:Thermodynamics; D014508:Urea / Q000737:chemistry
D011506:Proteins; D014508:Urea; D019791:Guanidine