Köper Ingo, Combet Sophie, Petry Winfried, Bellissent-Funel Marie-Claire
Laboratoire Léon-Brillouin UMR 12 CEA/CNRS, CEA/Saclay, 91191, Gif-sur-Yvette Cedex, France.
Eur Biophys J. 2008 Jul;37(6):739-48. doi: 10.1007/s00249-007-0248-x. Epub 2008 Jan 8.
The molecular understanding of protein stabilization by the disaccharide trehalose in extreme temperature or hydration conditions is still debated. In the present study, we investigated the role of trehalose on the dynamics of the protein C-phycocyanin (C-PC) by neutron scattering. To single out the motions of C-PC hydrogen (H) atoms in various trehalose/water environments, measurements were performed in deuterated trehalose and heavy water (D2O). We report that trehalose decreases the internal C-PC dynamics, as shown by a reduced diffusion coefficient of protein H atoms. By fitting the Elastic Incoherent Structure Factor--which gives access to the "geometry" of the internal proton motions--with the model of diffusion inside a sphere, we found that the presence of trehalose induces a significantly higher proportion of immobile C-PC hydrogens. We investigated, by elastic neutron scattering, the mean square displacements (MSDs) of deuterated trehalose/D2O-embedded C-PC as a function of temperature in the range of 40-318 K. Between 40 and approximately 225 K, harmonic MSDs of C-PC are slightly smaller in samples containing trehalose. Above a transition temperature of approximately 225 K, we observed anharmonic motions in all trehalose/water-coated C-PC samples. In the hydrated samples, MSDs are not significantly changed by addition of 15% trehalose but are slightly reduced by 30% trehalose. In opposition, no dynamical transition was detected in dry trehalose-embedded C-PC, whose hydrogen motions remain harmonic up to 318 K. These results suggest that a role of trehalose would be to stabilize proteins by inhibiting some fluctuations at the origin of protein unfolding and denaturation.
在极端温度或水合条件下,二糖海藻糖对蛋白质稳定性的分子理解仍存在争议。在本研究中,我们通过中子散射研究了海藻糖对蛋白质C-藻蓝蛋白(C-PC)动力学的作用。为了区分C-PC氢(H)原子在各种海藻糖/水环境中的运动,我们在氘代海藻糖和重水(D2O)中进行了测量。我们报告称,海藻糖降低了C-PC的内部动力学,这表现为蛋白质H原子的扩散系数降低。通过将能够获取内部质子运动“几何结构”的弹性非相干结构因子与球体内扩散模型进行拟合,我们发现海藻糖的存在导致了固定不动的C-PC氢原子比例显著更高。我们通过弹性中子散射研究了嵌入氘代海藻糖/D2O的C-PC的平均平方位移(MSD)随温度在40 - 318 K范围内的变化。在40至约225 K之间,含有海藻糖的样品中C-PC的简谐MSD略小。在约225 K的转变温度以上,我们在所有海藻糖/水包覆的C-PC样品中都观察到了非谐运动。在水合样品中,添加15%的海藻糖对MSD没有显著影响,但添加30%的海藻糖会使其略有降低。相反,在干燥的海藻糖嵌入的C-PC中未检测到动力学转变,其氢运动在高达318 K时仍保持简谐性。这些结果表明,海藻糖的作用可能是通过抑制蛋白质展开和变性起始处的一些波动来稳定蛋白质。