Centre Armand-Frappier Santé Biotechnologie, Institut national de la recherche scientifique (INRS), Université du Québec, 531 Boulevard des Prairies, Laval, QC H7V 1B7, Canada.
Centre Armand-Frappier Santé Biotechnologie, Institut national de la recherche scientifique (INRS), Université du Québec, 531 Boulevard des Prairies, Laval, QC H7V 1B7, Canada; Department of Chemistry, New Jersey City University, Jersey City, NJ 07305, USA.
Structure. 2023 Mar 2;31(3):329-342.e4. doi: 10.1016/j.str.2022.12.011. Epub 2023 Jan 16.
The evolutionary role of conformational exchange in the emergence and preservation of function within structural homologs remains elusive. While protein engineering has revealed the importance of flexibility in function, productive modulation of atomic-scale dynamics has only been achieved on a finite number of distinct folds. Allosteric control of unique members within dynamically diverse structural families requires a better appreciation of exchange phenomena. Here, we examined the functional and structural role of conformational exchange within eosinophil-associated ribonucleases. Biological and catalytic activity of various EARs was performed in parallel to mapping their conformational behavior on multiple timescales using NMR and computational analyses. Despite functional conservation and conformational seclusion to a specific domain, we show that EARs can display similar or distinct motional profiles, implying divergence rather than conservation of flexibility. Comparing progressively more distant enzymes should unravel how this subfamily has evolved new functions and/or altered their behavior at the molecular level.
构象交换在结构同源物中功能的出现和保留中的进化作用仍然难以捉摸。虽然蛋白质工程已经揭示了灵活性在功能中的重要性，但原子尺度动力学的有效调节仅在有限数量的不同折叠中实现。在动态多样的结构家族中对独特成员的变构控制需要更好地了解交换现象。在这里，我们研究了嗜酸性粒细胞相关核糖核酸酶中构象交换的功能和结构作用。使用 NMR 和计算分析，我们同时进行了各种 EAR 的生物学和催化活性的研究，并在多个时间尺度上对其构象行为进行了映射。尽管功能保守且构象隔离在特定的结构域中，但我们表明 EAR 可以显示相似或不同的运动特征，这意味着灵活性的发散而不是保守。比较越来越远的酶应该可以揭示这个亚家族如何进化出新的功能，或者在分子水平上改变它们的行为。
