Ever since Ranganathan and coworkers subjected the covariation of amino acid residues in the postsynaptic density-95/Discs large/Zonula occludens 1 (PDZ) domain family to a statistical correlation analysis, PDZ domains have represented a paradigmatic family to explore single domain protein allostery. Nevertheless, several theoretical and experimental studies in the past two decades have contributed contradicting results with regard to structural localization of the allosteric networks, or even questioned their actual existence in PDZ domains. In this review, we first describe theoretical and experimental approaches that were used to probe the energetic network(s) in PDZ domains. We then compare the proposed networks for two well-studied PDZ domains namely the third PDZ domain from PSD-95 and the second PDZ domain from PTP-BL. Our analysis highlights the contradiction between the different methods and calls for additional work to better understand these allosteric phenomena.

中文翻译：

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寻找 PDZ 域中的变构网络

自从 Ranganathan 和同事对突触后密度 95/Discs Large/Zonula occlusionns 1 (PDZ) 结构域家族中氨基酸残基的共变进行统计相关分析以来，PDZ 结构域就代表了探索单结构域蛋白质变构的典范家族。然而，过去二十年的一些理论和实验研究在变构网络的结构定位方面得出了相互矛盾的结果，甚至质疑它们在 PDZ 域中的实际存在。在这篇综述中，我们首先描述了用于探测 PDZ 域中能量网络的理论和实验方法。然后，我们比较了两个经过充分研究的 PDZ 域的拟议网络，即 PSD-95 中的第三个 PDZ 域和 PTP-BL 中的第二个 PDZ 域。我们的分析强调了不同方法之间的矛盾，并要求进行额外的工作以更好地理解这些变构现象。