title: Influence of pressure and crowding on the sub-nanosecond dynamics of globular proteins.
abstract: The influence of high hydrostatic pressure on the internal sub-nanosecond dynamics of highly concentrated lysozyme in aqueous solutions was studied by elastic incoherent neutron scattering (EINS) up to pressures of 4 kbar. We have found, with increasing pressure, a reduction in the dynamics of H atoms of folded lysozyme, suggesting a loss in protein mobility that follows a change in the local energy landscape upon the increase in packing density. Moreover, the amplitude of the protein fluctuations depends drastically on the protein concentration, and protein structural and interaction parameters as well as the dynamical properties are affected by pressure in a nonlinear way. A significant reduction of the mean squared displacement of H atoms occurs already at rather low pressures of a few hundred bars for lysozyme in bulk water solution. This trend is lifted at ∼2 kbar, which is probably due to a solvent-mediated effect. Conversely, for high protein concentrations (e.g., 160 mg mL(-1)), that is, under strong self-crowding conditions, as they are also encountered in the biological cell, strong restriction of the dynamics of protein motions takes place, reducing the mean squared displacement of H atoms by 60% and rendering its pressure dependence almost negligible. These results are also important for understanding the pressure stability of highly concentrated protein solutions in organisms thriving under hydrostatic pressure conditions such as in the deep sea, where pressures up to the kbar level are reached.
authors.affiliation: †Physical Chemistry I - Biophysical Chemistry, Department of Chemistry and Chemical Biology, TU Dortmund University, Otto-Hahn-Str. 6, 44227 Dortmund, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Erlkamp
authors.affiliation: ‡Université Grenoble Alpes, IBS, 71 avenue des Martyrs, CS 10090, 38044 Grenoble, France.|§Institut Laue-Langevin, 71 avenue des Martyrs, CS 20156, 38042 CEDEX 9 Grenoble, France.
authors.forename: J
authors.initials: J
authors.lastname: Marion
authors.affiliation: ‡Université Grenoble Alpes, IBS, 71 avenue des Martyrs, CS 10090, 38044 Grenoble, France.|§Institut Laue-Langevin, 71 avenue des Martyrs, CS 20156, 38042 CEDEX 9 Grenoble, France.
authors.forename: N
authors.initials: N
authors.lastname: Martinez
authors.affiliation: †Physical Chemistry I - Biophysical Chemistry, Department of Chemistry and Chemical Biology, TU Dortmund University, Otto-Hahn-Str. 6, 44227 Dortmund, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Czeslik
authors.affiliation: ‡Université Grenoble Alpes, IBS, 71 avenue des Martyrs, CS 10090, 38044 Grenoble, France.|§Institut Laue-Langevin, 71 avenue des Martyrs, CS 20156, 38042 CEDEX 9 Grenoble, France.
authors.forename: J
authors.initials: J
authors.lastname: Peters
authors.affiliation: †Physical Chemistry I - Biophysical Chemistry, Department of Chemistry and Chemical Biology, TU Dortmund University, Otto-Hahn-Str. 6, 44227 Dortmund, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Winter
mesh_terms: D000818:Animals; D008958:Models, Molecular; D009113:Muramidase / Q000737:chemistry / Q000378:metabolism*; D033363:Neutron Diffraction; D011312:Pressure; D011487:Protein Conformation
chemical_list: D009113:Muramidase