Centre for Crop and Disease Management, School of Molecular and Life Sciences, Curtin University, Perth, Australia.
Laboratoire des Interactions Plantes Micro-organismes Environnement (LIPME), INRAE, CNRS, Université de Toulouse, 31326, Castanet-Tolosan, France.
Nat Commun. 2023 Aug 28;14(1):5244. doi: 10.1038/s41467-023-40949-9.
Pathogens secrete effector proteins to subvert host physiology and cause disease. Effectors are engaged in a molecular arms race with the host resulting in conflicting evolutionary constraints to manipulate host cells without triggering immune responses. The molecular mechanisms allowing effectors to be at the same time robust and evolvable remain largely enigmatic. Here, we show that 62 conserved structure-related families encompass the majority of fungal orphan effector candidates in the Pezizomycotina subphylum. These effectors diversified through changes in patterns of thermodynamic frustration at surface residues. The underlying mutations tended to increase the robustness of the overall effector protein structure while switching potential binding interfaces. This mechanism could explain how conserved effector families maintained biological activity over long evolutionary timespans in different host environments and provides a model for the emergence of sequence-unrelated effector families with conserved structures.
病原体分泌效应蛋白来颠覆宿主生理学并导致疾病。效应物与宿主进行分子军备竞赛，导致在不引发免疫反应的情况下操纵宿主细胞的进化约束相互冲突。允许效应物同时具有稳健性和可进化性的分子机制在很大程度上仍是个谜。在这里，我们表明，在 Pezizomycotina 亚门中，62 个保守的结构相关家族包含了大多数真菌孤儿效应子候选物。这些效应子通过改变表面残基的热力学障碍模式而多样化。潜在的突变倾向于增加整个效应蛋白结构的稳健性，同时切换潜在的结合界面。这种机制可以解释为什么在不同的宿主环境中，保守的效应子家族能够在很长的进化时间内保持生物活性，并为具有保守结构的序列无关的效应子家族的出现提供了一个模型。
