Jülich Centre for Neutron Science JCNS and Institute for Complex Systems ICS, Forschungszentrum Jülich GmbH, 52425 Jülich, Germany.
Phys Chem Chem Phys. 2018 Feb 14;20(7):5128-5139. doi: 10.1039/c7cp08292d.
A characteristic property of unfolded and disordered proteins is their high molecular flexibility, which enables the exploration of a large conformational space. We present neutron scattering experiments on the dynamics of denatured and native folded bovine serum albumin (BSA) in solution. Global protein diffusion and internal macromolecular dynamics were measured using quasielastic neutron time-of-flight and backscattering spectroscopy on the picosecond to nanosecond time- and Ångstrom length-scale. Internal protein dynamics were analysed in a first approach using stretched exponential functions. In denatured BSA predominantly slow heterogeneous dynamics dominates the observed macromolecular motions. Reduction of disulphide bridges in denatured BSA does not significantly alter the visible motions. In native folded BSA fast homogeneous dynamics and slow heterogeneous dynamics were observed. In an alternative data analysis approach, internal protein dynamics was interpreted using the analytical model of the overdamped Brownian oscillator, which allowed us to extract mean square displacements of protein internal dynamics and the fraction of hydrogen atoms participating in the observed motions. Our results demonstrate that denaturation modifies the physical nature of internal protein dynamics significantly as compared to the native folded structure.
未折叠和无规蛋白质的一个特征性质是其具有高分子柔韧性，这使其能够探索很大的构象空间。我们在溶液中对变性和天然折叠的牛血清白蛋白（BSA）的动力学进行了中子散射实验。通过使用皮秒到纳秒时间和埃长度尺度的准弹性中子飞行时间和背散射光谱，测量了全局蛋白质扩散和内部大分子动力学。在初步分析中，使用扩展指数函数分析内部蛋白质动力学。在变性 BSA 中，主要是慢异质动力学主导观察到的大分子运动。在变性 BSA 中还原二硫键不会显著改变可见运动。在天然折叠的 BSA 中，观察到快速均相动力学和缓慢异质动力学。在另一种数据分析方法中，使用受迫布朗振荡器的分析模型解释内部蛋白质动力学，这使我们能够提取蛋白质内部动力学的均方位移和参与观察运动的氢原子分数。我们的结果表明，与天然折叠结构相比，变性会显著改变内部蛋白质动力学的物理性质。
