Jülich Centre for Neutron Science (JCNS-1) and Institute of Biological Information Processing (IBI-8), Forschungszentrum Jülich GmbH, 52425 Jülich, Germany.
Institute of Physical Chemistry, RWTH Aachen University, Landoltweg 2, 52056 Aachen, Germany.
Int J Mol Sci. 2022 Jun 23;23(13):6969. doi: 10.3390/ijms23136969.
Myelin basic protein (MBP) is intrinsically disordered in solution and is considered as a conformationally flexible biomacromolecule. Here, we present a study on perturbation of MBP structure and dynamics by the denaturant guanidinium chloride (GndCl) using small-angle scattering and neutron spin-echo spectroscopy (NSE). A concentration of 0.2 M GndCl causes charge screening in MBP resulting in a compact, but still disordered protein conformation, while GndCl concentrations above 1 M lead to structural expansion and swelling of MBP. NSE data of MBP were analyzed using the Zimm model with internal friction (ZIF) and normal mode (NM) analysis. A significant contribution of internal friction was found in compact states of MBP that approaches a non-vanishing internal friction relaxation time of approximately 40 ns at high GndCl concentrations. NM analysis demonstrates that the relaxation rates of internal modes of MBP remain unaffected by GndCl, while structural expansion due to GndCl results in increased amplitudes of internal motions. Within the model of the Brownian oscillator our observations can be rationalized by a loss of friction within the protein due to structural expansion. Our study highlights the intimate coupling of structural and dynamical plasticity of MBP, and its fundamental difference to the behavior of ideal polymers in solution.
髓鞘碱性蛋白（MBP）在溶液中结构无序，被认为是一种构象柔性生物大分子。在这里，我们使用小角散射和中子自旋回波谱（NSE）研究了变性剂盐酸胍（GndCl）对 MBP 结构和动力学的干扰。0.2 M GndCl 浓度导致 MBP 中的电荷屏蔽，从而导致其形成紧凑但仍然无序的蛋白质构象，而 GndCl 浓度高于 1 M 则导致 MBP 的结构膨胀和肿胀。我们使用内耗（ZIF）和正常模式（NM）分析的 Zimm 模型分析了 MBP 的 NSE 数据。在 MBP 的紧凑状态下发现了显著的内耗贡献，在高 GndCl 浓度下，内耗弛豫时间接近 40 ns。NM 分析表明，GndCl 对内部分子运动的弛豫速率没有影响，而 GndCl 引起的结构膨胀导致内部分子运动的幅度增加。在布朗振荡器模型中，我们的观察结果可以用由于结构膨胀导致的蛋白质内摩擦力的损失来合理化。我们的研究强调了 MBP 结构和动力学可塑性的紧密耦合，以及其与溶液中理想聚合物行为的根本区别。
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