CzrA转录抑制因子的多尺度分析揭示金属离子结合诱导的别构变化
A multi-scale analysis of the CzrA transcription repressor highlights the allosteric changes induced by metal ion binding
AI总结：
本文利用微秒级MD轨迹与MEOW信息论方法分析CzrA，揭示锌配位状态如何引发DNA结合区域及全分子的别构构象变化。
摘要：
别构调控是多种蛋白质用于转导化学信号并执行生物学功能的一种广泛策略。金属感应蛋白在这方面具有代表性，例如，它们会根据远端离子配位位点的状态选择性地结合和解离DNA。在本研究中，我们通过分析微秒级分子动力学（MD）轨迹，对CzrA转录抑制因子的结构和力学性质进行了研究；这些轨迹通过mapping entropy optimisation workflow（MEOW，映射熵优化工作流）进行处理，这是一种近期开发的信息论方法，能够以无监督方式凸显具有特殊力学、功能和生物学重要性的残基。该方法使我们得以揭示分子性质的差异如何受锌配位位点状态控制，并特别关注DNA结合区域。这些变化与整个分子中残基构象可变性的重新分布相关，尽管在离子结合和游离这两种配位状态下，分子的整体架构保持一致。本研究结果证实了以往的研究，为CzrA力学的精细细节提供了新的见解，并展示MEOW方法可作为一种新工具，通过分析普通MD模拟来研究蛋白质中的别构调控及其他过程。
英文摘要：
Allosteric regulation is a widespread strategy employed by several proteins to transduce chemical signals and perform biological functions. Metal sensor proteins are exemplary in this respect, e.g., in that they selectively bind and unbind DNA depending on the state of a distal ion coordination site. In this work, we carry out an investigation of the structural and mechanical properties of the CzrA transcription repressor through the analysis of microsecond-long molecular dynamics (MD) trajectories; the latter are processed through the mapping entropy optimisation workflow (MEOW), a recently developed information-theoretical method that highlights, in an unsupervised manner, residues of particular mechanical, functional, and biological importance. This approach allows us to unveil how differences in the properties of the molecule are controlled by the state of the zinc coordination site, with particular attention to the DNA binding region. These changes correlate with a redistribution of the conformational variability of the residues throughout the molecule, in spite of an overall consistency of its architecture in the two (ion-bound and free) coordination states. The results of this work corroborate previous studies, provide novel insight into the fine details of the mechanics of CzrA, and showcase the MEOW approach as a novel instrument for the study of allosteric regulation and other processes in proteins through the analysis of plain MD simulations.
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