Intermolecular correlations are necessary to explain diffuse scattering from protein crystals.
Intermolecular correlations are necessary to explain diffuse scattering from protein crystals.
复制标题
分子间相关性对于解释蛋白质晶体的漫散射是必要的。
DOI：
10.1107/s2052252518001124
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发表时间：
2018
期刊：
影响因子：
3.9
通讯作者：
Lane,ThomasJ
中科院分区：
文献类型：
--
作者：
Peck,Ariana;Poitevin,Frédéric;Lane,ThomasJ
构象变化驱动蛋白质的功能，包括催化、变构和信号传递。蛋白质晶体的X射线漫散射经常被认为是这些相关运动的探测器，具有极大的潜力促进我们对生物动力学的理解。然而，最近的工作对这一主流观点提出了挑战，相反，漫射散射主要源于刚体运动，因此可以应用于改进结构确定。为了研究引起扩散散射的无序的性质，从而研究这种信号的潜在应用，评估了一系列不同的无序模型的能力，以确定它是否能够再现从三个蛋白质晶体重建的扩散信号。这种比较表明，分子内构象动力学的多种模型，包括从布拉格数据推断的系综模型，都不能解释这一信号。刚体或短程类液体运动的模型，其中动力学被限制在生物单位，显示出与漫射图的适度一致，但无法再现表明长期相关性的实验特征。将类液体运动的模型扩展到包括晶体中邻近蛋白质的无序，显着提高了与所有三个系统的一致性，并突出了分子间相关性对观察信号的贡献。这些发现预计需要解释分子间的无序，以便推进扩散散射的解释，以提取生物运动或帮助结构推断。
Conformational changes drive protein function, including catalysis, allostery and signaling. X-ray diffuse scattering from protein crystals has frequently been cited as a probe of these correlated motions, with significant potential to advance our understanding of biological dynamics. However, recent work has challenged this prevailing view, suggesting instead that diffuse scattering primarily originates from rigid-body motions and could therefore be applied to improve structure determination. To investigate the nature of the disorder giving rise to diffuse scattering, and thus the potential applications of this signal, a diverse repertoire of disorder models was assessed for its ability to reproduce the diffuse signal reconstructed from three protein crystals. This comparison revealed that multiple models of intramolecular conformational dynamics, including ensemble models inferred from the Bragg data, could not explain the signal. Models of rigid-body or short-range liquid-like motions, in which dynamics are confined to the biological unit, showed modest agreement with the diffuse maps, but were unable to reproduce experimental features indicative of long-range correlations. Extending a model of liquid-like motions to include disorder across neighboring proteins in the crystal significantly improved agreement with all three systems and highlighted the contribution of intermolecular correlations to the observed signal. These findings anticipate a need to account for intermolecular disorder in order to advance the interpretation of diffuse scattering to either extract biological motions or aid structural inference.