College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Building 14, Dubai Health Care City, Dubai P.O. Box 505055, United Arab Emirates.
Int J Mol Sci. 2022 Oct 1;23(19):11606. doi: 10.3390/ijms231911606.
The actin cytoskeleton lies at the heart of many essential cellular processes. There are hundreds of proteins that cells use to control the size and shape of actin cytoskeletal networks. As such, various pathogens utilize different strategies to hijack the infected eukaryotic host actin dynamics for their benefit. These include the control of upstream signaling pathways that lead to actin assembly, control of eukaryotic actin assembly factors, encoding toxins that distort regular actin dynamics, or by encoding effectors that directly interact with and assemble actin filaments. The latter class of effectors is unique in that, quite often, they assemble actin in a straightforward manner using novel sequences, folds, and molecular mechanisms. The study of these mechanisms promises to provide major insights into the fundamental determinants of actin assembly, as well as a deeper understanding of host-pathogen interactions in general, and contribute to therapeutic development efforts targeting their respective pathogens. This review discusses mechanisms and highlights shared and unique features of actin assembly by pathogen effectors that directly bind and assemble actin, focusing on eukaryotic actin nucleator functional mimics Sca2 (formin mimic), BimA (Ena/VASP mimic), and VopL (tandem WH2-motif mimic).
肌动蛋白细胞骨架位于许多基本细胞过程的核心。细胞使用数百种蛋白质来控制肌动蛋白细胞骨架网络的大小和形状。因此，各种病原体利用不同的策略来劫持受感染的真核宿主肌动蛋白动力学以谋取利益。这些策略包括控制导致肌动蛋白组装的上游信号通路，控制真核肌动蛋白组装因子，编码扭曲正常肌动蛋白动力学的毒素，或编码直接与肌动蛋白丝相互作用和组装的效应物。后一类效应物的独特之处在于，它们经常使用新颖的序列、折叠和分子机制直接组装肌动蛋白。这些机制的研究有望为肌动蛋白组装的基本决定因素提供重要的见解，同时更深入地了解宿主-病原体相互作用，并为靶向各自病原体的治疗开发努力做出贡献。本文讨论了机制，并强调了直接结合和组装肌动蛋白的病原体效应物的肌动蛋白组装的共享和独特特征，重点介绍了真核肌动蛋白成核功能模拟物 Sca2（formin 模拟物）、BimA（Ena/VASP 模拟物）和 VopL（串联 WH2 基序模拟物）。
