Browsing by Author "Weik, M"

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    Dynamical coupling of intrinsically disordered proteins and their hydration water: comparison with folded soluble and membrane proteins
    (Cell Press, 2012-07-03) Gallat, FX; Laganowsky, A; Wood, K; Gabel, F; van Eijck, L; Wuttke, J; Moulin, M; Haertlein, M; Eisenberg, D; Colletier, JP; Zaccai, G; Weik, M
    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. © 2012, Cell Press.
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    Low-temperature inflection observed in neutron scattering measurements of proteins is due to methyl rotation: direct evidence using isotope labeling and molecular dynamics simulations
    (American Chemical Society, 2010-04-14) Wood, K; Tobias, DJ; Kessler, B; Gabel, F; Oesterhelt, D; Mulder, FAA; Zaccai, G; Weik, M
    There is increasing interest in the contribution of methyl groups to the overall dynamics measured by neutron scattering experiments of proteins. In particular an inflection observed in atomic mean square displacements measured as a function of temperature on high resolution spectrometers (~1 μeV) was explained by the onset of methyl group rotations. By specifically labeling a non-methyl-containing side-chain in a native protein system, the purple membrane, and performing neutron scattering measurements, we here provide direct experimental evidence that the observed inflection is indeed due to methyl group rotations. Molecular dynamics simulations reproduce the experimental data, and their analysis suggests that the apparent transition is due to methyl group rotation entering the finite instrumental resolution of the spectrometer. Methyl group correlation times measured by solid state NMR in the purple membrane, taken from previous work, support the interpretation. © 2010, American Chemical Society
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    Protein surface and core dynamics show concerted hydration-dependent activation
    (Wiley-V C H Verlag GMBH, 2013-01-01) Wood, K; Gallat, FX; Otten, R; van Heel, AJ; Lethier, M; van Eijck, L; Moulin, M; Haertlein, M; Weik, M; Mulder, FAA
    By specifically labeling leucine/valine methyl groups and lysine side chains “inside” and “outside” dynamics of proteins on the nanosecond timescale are compared using neutron scattering (see picture). Surprisingly, both groups display similar dynamics as a function of temperature, and the buried hydrophobic core is sensitive to hydration and undergoes a dynamical transition. © 2013, Wiley-VCH Verlag GmbH & Co. KGaA