Browsing by Author "Zaccai, G"
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- ItemDynamical 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, MHydration 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.
- ItemLow-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, MThere 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
- ItemNew sources and instrumentation for neutrons in biology(Elsevier, 2008-04-18) Teixeira, SCM; Zaccai, G; Ankner, J; Bellissent-Funel, MC; Bewley, RI; Blakeley, MP; Callow, P; Coates, L; Dahint, R; Dalgliesh, R; Dencher, NA; Forsyth, VT; Fragneto, G; Frick, B; Gilles, R; Gutberlet, T; Haertlein, M; Hauß, T; Häußler, W; Heller, WT; Herwig, K; Holderer, O; Juranyi, F; Kampmann, R; Knott, RB; Krueger, S; Langan, P; Lechner, RE; Lynn, GW; Majkrzak, CF; May, RP; Meilleur, F; Mo, Y; Mortensen, K; Myles, DAA; Natali, F; Neylon, C; Niimura, N; Ollivier, J; Ostermann, A; Peters, J; Pieper, J; Rühm, A; Schwahn, D; Shibata, K; Soper, AK; Strässle, T; Suzuki, J; Tanaka, I; Tehei, M; Timmins, P; Torikai, N; Unruh, T; Urban, V; Vavrin, R; Weiss, KNeutron radiation offers significant advantages for the study of biological molecular structure and dynamics. A broad and significant effort towards instrumental and methodological development to facilitate biology experiments at neutron sources worldwide is reviewed. © 2008, Elsevier Ltd.
- ItemPicosecond dynamics in haemoglobin from different species: a quasielastic neutron scattering study(Elsevier, 2014-10) Stadler, AM; Garvey, CJ; Embs, JP; Koza, MM; Unruh, T; Artmann, GM; Zaccai, GBackground Dynamics in haemoglobin from platypus (Ornithorhynchus anatinus), chicken (Gallus gallus domesticus) and saltwater crocodile (Crocodylus porosus) were measured to investigate response of conformational motions on the picosecond time scale to naturally occurring variations in the amino acid sequence of structurally identical proteins. Methods Protein dynamics was measured using incoherent quasielastic neutron scattering. The quasielastic broadening was interpreted first with a simple single Lorentzian approach and then by using the Kneller–Volino Brownian dynamics model. Results Mean square displacements of conformational motions, diffusion coefficients of internal dynamics and residence times for jump-diffusion between sites and corresponding effective force constants (resilience) and activation energies were determined from the data. Conclusions Modifications of the physicochemical properties caused by mutations of the amino acids were found to have a significant impact on protein dynamics. Activation energies of local side chain dynamics were found to be similar between the different proteins being close to the energy, which is required for the rupture of single hydrogen bond in a protein. General significance The measured dynamic quantities showed significant and systematic variations between the investigated species, suggesting that they are the signature of an evolutionary adaptation process stimulated by the different physiological environments of the respective protein. © 2014,Elsevier B.V.
- ItemSpecific cellular water dynamics observed in vivo by neutron scattering and NMR(Royal Society of Chemistry, 2010-09-21) Jasnin, M; Stadler, A; Tehei, M; Zaccai, GNeutron scattering, by using deuterium labelling, revealed how intracellular water dynamics, measured in vivo in E. coli, human red blood cells and the extreme halophile, Haloarcula marismortui, depends on the cell type and nature of the cytoplasm. The method uniquely permits the determination of motions on the molecular length (~ ångstrøm) and time (pico- to nanosecond) scales. In the bacterial and human cells, intracellular water beyond the hydration shells of cytoplasmic macromolecules and membrane faces flows as freely as liquid water. It is not "tamed" by confinement. In contrast, in the extreme halophile archaeon, in addition to free and hydration water an intracellular water component was observed with significantly slowed down translational diffusion. The results are discussed and compared to observations in E. coli and Haloarcula marismortui by deuteron spin relaxation in NMR—a method that is sensitive to water rotational dynamics on a wide range of time scales. © 2010, Royal Society of Chemistry
- ItemThermal fluctuations of haemoglobin from different species: adaptation to temperature via conformational dynamics(The Royal Society, 2012-11-07) Stadler, AM; Garvey, CJ; Bocahut, A; Sacquin-Mora, S; Digel, I; Schneider, GJ; Natali, F; Artmann, GM; Zaccai, GThermodynamic stability, configurational motions and internal forces of haemoglobin (Hb) of three endotherms (platypus, Ornithorhynchus anatinus; domestic chicken, Gallus gallus domesticus and human, Homo sapiens) and an ectotherm (salt water crocodile, Crocodylus porosus) were investigated using circular dichroism, incoherent elastic neutron scattering and coarse-grained Brownian dynamics simulations. The experimental results from Hb solutions revealed a direct correlation between protein resilience, melting temperature and average body temperature of the different species on the 0.1 ns time scale. Molecular forces appeared to be adapted to permit conformational fluctuations with a root mean square displacement close to 1.2 Å at the corresponding average body temperature of the endotherms. Strong forces within crocodile Hb maintain the amplitudes of motion within a narrow limit over the entire temperature range in which the animal lives. In fully hydrated powder samples of human and chicken, Hb mean square displacements and effective force constants on the 1 ns time scale showed no differences over the whole temperature range from 10 to 300 K, in contrast to the solution case. A complementary result of the study, therefore, is that one hydration layer is not sufficient to activate all conformational fluctuations of Hb in the pico- to nanosecond time scale which might be relevant for biological function. Coarse-grained Brownian dynamics simulations permitted to explore residue-specific effects. They indicated that temperature sensing of human and chicken Hb occurs mainly at residues lining internal cavities in the β-subunits. Copyright © The Royal Society 2012.