Relevance of Internal Friction and Structural Constraints for the Dynamics of Denatured Bovine Serum Albumin

• DOI: 10.1021/acs.jpclett.8b00825
• Publication Date: 2018-04-24T18:23:04Z
• Authors: Felix Ameseder; Aurel Radulescu; Olaf Holderer; Peter Falus; Dieter Richter; Andreas M. Stadler
• Keywords: Neutron Diffraction; Protein Denaturation; 0303 health sciences; 03 medical and health sciences; Circular Dichroism; Scattering, Small Angle; Hydrodynamics; Animals; Cattle; Serum Albumin, Bovine; Dynamic Light Scattering; Guanidine

A general property of disordered proteins is their structural expansion that results in a high molecular flexibility. The structure and dynamics of bovine serum albumin (BSA) denatured by guanidinium hydrochloride (GndCl) were investigated using small-angle neutron scattering (SANS) and neutron spin-echo spectroscopy (NSE). SANS experiments demonstrated the relevance of intrachain interactions for structural expansion. Using NSE experiments, we observed a high internal flexibility of denatured BSA in addition to center-of-mass diffusion detected by dynamic light scattering. Internal motions measured by NSE were described using concepts based on polymer theory. The contribution of residue-solvent friction was accounted for using the Zimm model including internal friction (ZIF). Disulfide bonds forming loops of amino acids of the peptide backbone have a major impact on internal dynamics that can be interpreted with a reduced set of Zimm modes.