Friction-Limited Folding of Disulfide-Reduced Monomeric SOD1.

Friction-Limited Folding of Disulfide-Reduced Monomeric SOD1.
Biophys J. 2020 Mar 12;:
Authors: Cohen NR, Kayatekin C, Zitzewitz JA, Bilsel O, Matthews CR
Abstract
The folding reaction of a stable monomeric variant of Cu/Zn superoxide dismutase (mSOD1), an enzyme responsible for the conversion of superoxide free radicals into hydrogen peroxide and oxygen, is known to be among the slowest folding processes that adhere to two-state behavior. The long lifetime, ∼10 s, of the unfolded state presents ample opportunities for the polypeptide chain to transiently sample nonnative structures before the formation of the productive folding transition state. We recently observed the formation of a nonnative structure in a peptide model of the C-terminus of SOD1, a sequence that might serve as a potential source of internal chain friction-limited folding. To test for friction-limited folding, we performed a comprehensive thermodynamic and kinetic analysis of the folding mechanism of mSOD1 in the presence of the viscogens glycerol and glucose. Using a, to our knowledge, novel analysis of the folding reactions, we found the disulfide-reduced form of the protein that exposes the C-terminal sequence, but not its disulfide-oxidized counterpart that protects it, experiences internal chain friction during folding. The sensitivity of the internal friction to the disulfide bond status suggests that one or both of the cross-linked regions play a critical...

Source: Biophysical Journal - March 11, 2020 Category: Physics Authors: Cohen NR, Kayatekin C, Zitzewitz JA, Bilsel O, Matthews CR Tags: Biophys J Source Type: research