Dynamical Coupling of Intrinsically Disordered Proteins and Their Hydration Water: Comparison with Folded Soluble and Membrane Proteins

Abstract

Hydration water is vital for various macromolecular biological activities, such as specific ligand recognition, enzyme activity, response to receptor binding, and energy transduction. Without hydration water, proteins would not fold correctly and would lack the conformational flexibility that animates their three-dimensional structures. Motions in globular, soluble proteins are thought to be governed to a certain extent by hydration-water dynamics, yet it is not known whether this relationship holds true for other protein classes in general and whether, in turn, the structural nature of a protein also influences water motions. Here, we provide insight into the coupling between hydration-water dynamics and atomic motions in intrinsically disordered proteins (IDP), a largely unexplored class of proteins that, in contrast to folded proteins, lack a well-defined three-dimensional structure. We investigated the human IDP tau, which is involved in the pathogenic processes accompanying Alzheimer disease. Combining neutron scattering and protein perdeuteration, we found similar atomic mean-square displacements over a large temperature range for the tau protein and its hydration water, indicating intimate coupling between them. This is in contrast to the behavior of folded proteins of similar molecular weight, such as the globular, soluble maltose-binding protein and the membrane protein bacteriorhodopsin, which display moderate to weak coupling, respectively. The extracted mean square displacements also reveal a greater motional flexibility of IDP compared with globular, folded proteins and more restricted water motions on the IDP surface. The results provide evidence that protein and hydration-water motions mutually affect and shape each other, and that there is a gradient of coupling across different protein classes that may play a functional role in macromolecular activity in a cellular context.

Hydration water mobility is enhanced around tau amyloid fibers

“…The expression and purification of the human isoform htau40 has been published elsewhere (13) and is briefly recalled in SI Materials and Methods. The deuterated fibers (denoted as D-fiber) and hydrogenated fibers (H-fiber) were prepared identically.…”

“…It mediates protein−protein and protein−DNA recognition, is involved in allostery, partakes in enzymatic reactions and proton and electron transfer, and more generally plasticizes biological macromolecules by providing their surface with an extensive and highly dynamic network of hydrogen bonds. Compared with folded proteins, tau has been shown to have a stronger coupling with its hydration water (13). However, very little is known about the role water plays in protein aggregation in general and in tau fibrillation in particular.…”

Dynamic footprint of sequestration in the molecular fluctuations of osteopontin

“…Despite these limitations the apparent MSD technique has nonetheless been proved useful to compare the dynamics of different classes of proteins. Gallat et al [47] showed that the intrinsically disordered tau protein behaves in a more dynamic manner compared with MBP, a globular protein of similar molecular mass. The conclusions, drawn by Gallat and co-workers, that a disordered protein behaves more dynamically then a folded counterpart, have been confirmed by quasi-elastic neutron studies of the intrinsically disordered b-casein [70,71].…”

“…Tau was chosen for comparison to an IDP, while the MBP provides a comparison to a globular protein of a similar size (both taken from Gallat et al [47]). Dynamine functions by comparing sequence information with a database of recorded NMR spectra.…”

“…This quantity can be obtained more easily than a full spectrum and provides information via an integral number of the amount of elastic scattering 'lost' due to the molecular mobility in the sample [22,46]. This technique is often used to obtain comparative information about protein dynamics in hydrated powders [47,48]. We focus on this apparent MSD technique regarding the protein dynamics in the present work, but will also discuss known limitations.…”