Variation of Structural and Dynamical Flexibility of Myelin Basic Protein in Response to Guanidinium Chloride

Abstract

Myelin basic protein (MBP) is intrinsically disordered in solution and is considered as a conformationally flexible biomacromolecule. Here, we present a study on perturbation of MBP structure and dynamics by the denaturant guanidinium chloride (GndCl) using small-angle scattering and neutron spin–echo spectroscopy (NSE). A concentration of 0.2 M GndCl causes charge screening in MBP resulting in a compact, but still disordered protein conformation, while GndCl concentrations above 1 M lead to structural expansion and swelling of MBP. NSE data of MBP were analyzed using the Zimm model with internal friction (ZIF) and normal mode (NM) analysis. A significant contribution of internal friction was found in compact states of MBP that approaches a non-vanishing internal friction relaxation time of approximately 40 ns at high GndCl concentrations. NM analysis demonstrates that the relaxation rates of internal modes of MBP remain unaffected by GndCl, while structural expansion due to GndCl results in increased amplitudes of internal motions. Within the model of the Brownian oscillator our observations can be rationalized by a loss of friction within the protein due to structural expansion. Our study highlights the intimate coupling of structural and dynamical plasticity of MBP, and its fundamental difference to the behavior of ideal polymers in solution.

Dynamics of Single-Chain Nanoparticles under Crowding: A Neutron Spin Echo Study

“…Previous NSE studies on the dynamics of SCNPs in dilute solutions revealed the relaxation of internal degrees of freedom, but clearly slowed down with respect to their linear precursor counterparts. , This effect is attributed to the internal friction associated with the compartmentalization in domains within the macromolecule. To describe the dynamic structure factor, the dual polymer/NP character of the SCNPs in solution was considered by applying theoretical approximations based on the Zimm model. , Similar dynamic behavior has been found from NSE investigations on solutions of IDPs and protein chains unfolded by denaturing, − with a relatively large contribution of internal dynamics to the overall diffusion but a slowing down of the more local modes. This effect can be taken into account by adding an internal friction and is essentially the same effect found in SCNPs.…”

Applications of neutron spin echo in soft matter

“…They also found the same densification behavior of MBP. The difference was that at high concentrations of GndCl, MBP exhibited repulsive intra-chain interactions, with structure swelled and relaxation time increased [61]. The emerging field of intrinsically disordered proteins expands our understanding of protein structure-function relationships and emphasizes the importance of protein flexibility and conformational variability in cellular processes.…”