Structure and Dynamics of Intrinsically Disordered and Unfolded Proteins: Investigations using Small-Angle Scattering and Neutron Spin-Echo Spectroscopy

Abstract

A characteristic property of intrinsically disordered and unfolded proteins is their high molecular flexibility, which enables the exploration of a large conformational space. We present neutron scattering experiments on the structure and dynamics of the intrinsically disordered myelin basic protein (MBP) and the chemically denatured bovine serum albumin (BSA) in solution. Small-angle neutron scattering (SANS) experiments allowed us to gain information of structural aspects of MBP and denatured BSA as response to denaturant conditions. Using neutron spin-echo spectroscopy (NSE), we were able to investigate collective motions of the protein chain up to several hundred nanoseconds on the nanometre length-scale. NSE results showed a high flexibility of the unfolded proteins. Internal motions of the intrinsically disordered MBP and denatured BSA were described using normal mode analysis and concepts derived from polymer theory. The contribution of residue-solvent friction was accounted for using the Zimm model including internal friction. Motions of MBP are well described by collective normal modes, while dynamics of denatured BSA shows polymer-like properties. Disulphide bonds forming loops of amino acids of the peptide backbone have a major impact on internal dynamics of denatured BSA that can be interpreted with a reduced set of Zimm modes.