Dynamics of well-folded and natively disordered proteins in solution: a time-of-flight neutron scattering study

Abstract

Casein proteins belong to the class of natively disordered proteins. The existence of disordered biologically active proteins questions the assumption that a well-folded structure is required for function. A hypothesis generally put forward is that the unstructured nature of these proteins results from the functional need of a higher flexibility. This interplay between structure and dynamics was investigated in a series of time-of-flight neutron scattering experiments, performed on casein proteins, as well as on three well-folded proteins with distinct secondary structures, namely, myoglobin (alpha), lysozyme (alpha/beta) and concanavalin A (beta). To illustrate the subtraction of the solvent contribution from the scattering spectra, we used the dynamic susceptibility spectra emphasizing the high frequency part of the spectrum, where the solvent dominates. The quality of the procedure is checked by comparing the corrected spectra to those of the dry and hydrated protein with negligible solvent contamination. Results of spectra analysis reveal differences in motional amplitudes of well-folded proteins, where beta-sheet structures appear to be more rigid than a cluster of alpha-helices. The disordered caseins display the largest conformational displacements. Moreover their global diffusion rates deviate from the expected dependence, suggesting further large-scale conformational motions.

Neutron Spin-Echo and TOF Reveals Protein Dynamics in Solution

“…The scattering signal, however, stems from protons of the protein and thus indicates the presence of dangling (side) groups. The results are in some variance to findings from TOF experiments on small globular proteins (lysozyme and concanavalin A) and disordered proteins (caseins) [9]. For those besides diffusion a Q-independent local fast component with a width of 0.15 meV (τ 4 ps) was found virtually independent of the protein type.…”

Rigidity of transmembrane proteins determines their cluster shape

“…These results show that RPs are torsionally stiffer than SFPs. Our findings are consistent with the higher conformational displacements of α-helices compared to β-sheets [11,27]. In all of our simulations, the effect of hydrophobic mismatch is neutralized, ∆r = 0.01, by using the HT 5 H model proteins.…”

Introduction to Quasielastic Neutron Scattering

“…Gaspar et al [44] investigated the interplay between structure and dynamics of different proteins using TOF-techniques. They scrutinized casein proteins (belonging to the class of natively disordered proteins) and in addition three wellfolded proteins with distinct secondary structures (myoglobin, lysozyme and concanavalin A).…”