Interesting Biochemistries in the Structure and Function of Bacterial Effectors.
Interesting Biochemistries in the Structure and Function of Bacterial Effectors.
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在细菌效应器的结构和功能有趣的生物化学。
DOI：
10.3389/fcimb.2021.608860
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发表时间：
2021
影响因子：
5.7
通讯作者：
Thurston TLM
中科院分区：
文献类型：
--
作者：
Mak H;Thurston TLM
细菌效应蛋白通过多蛋白分泌系统传递到宿主细胞中，是细菌发病的重要媒介。递送后，它们调节宿主细胞的一系列过程和功能。强大的选择压力导致细菌效应物进化出独特的结构，可以模仿宿主蛋白质的生化活性或实现新的和独特的生物化学。尽管存在蛋白质结构-功能范式，但来自不同细菌物种的效应器具有相同的生化活性，例如泛素与底物的偶联，并不一定具有彼此或执行相同功能的真核蛋白的结构或序列同源性。此外，一些细菌效应物已经进化成已知的蛋白质折叠结构变异，从而实现不同或额外的生化和生理功能。尽管与真核生物蛋白质组相比，原核蛋白质组中内在无序蛋白或区域的总体发生率较低，但细菌效应物似乎采用了模仿真核生物信号蛋白无序区域的内在无序区域。在这篇综述中，我们探讨了在细菌效应物中发现的多种生化特性的例子，这些特性使效应物介导的真核信号通路干扰并最终支持发病机制。尽管在效应器的结构和功能表征方面存在挑战，但最近在理解这些毒力因子促进发病机制的通常不寻常和迷人的方式方面取得了进展。然而，为了揭示效应器所显示的一系列显著活动，继续开展工作是必不可少的。
Bacterial effector proteins, delivered into host cells by specialized multiprotein secretion systems, are a key mediator of bacterial pathogenesis. Following delivery, they modulate a range of host cellular processes and functions. Strong selective pressures have resulted in bacterial effectors evolving unique structures that can mimic host protein biochemical activity or enable novel and distinct biochemistries. Despite the protein structure-function paradigm, effectors from different bacterial species that share biochemical activities, such as the conjugation of ubiquitin to a substrate, do not necessarily share structural or sequence homology to each other or the eukaryotic proteins that carry out the same function. Furthermore, some bacterial effectors have evolved structural variations to known protein folds which enable different or additional biochemical and physiological functions. Despite the overall low occurrence of intrinsically disordered proteins or regions in prokaryotic proteomes compared to eukaryotes proteomes, bacterial effectors appear to have adopted intrinsically disordered regions that mimic the disordered regions of eukaryotic signaling proteins. In this review, we explore examples of the diverse biochemical properties found in bacterial effectors that enable effector-mediated interference of eukaryotic signaling pathways and ultimately support pathogenesis. Despite challenges in the structural and functional characterisation of effectors, recent progress has been made in understanding the often unusual and fascinating ways in which these virulence factors promote pathogenesis. Nevertheless, continued work is essential to reveal the array of remarkable activities displayed by effectors.