A glycine-rich PE_PGRS protein governs mycobacterial actin-based motility.
A glycine-rich PE_PGRS protein governs mycobacterial actin-based motility.
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富含甘氨酸的PE_PGRS蛋白控制分枝杆菌基于肌动蛋白的运动。
DOI：
10.1038/s41467-022-31333-0
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发表时间：
2022-06-24
影响因子：
16.6
通讯作者：
Welch MD
中科院分区：
文献类型：
--
作者：
Hill NS;Welch MD
通过研究微生物病原体在感染期间如何拦截肌动蛋白细胞骨架，获得了许多关于肌动蛋白调控的关键见解。海洋分枝杆菌是人类结核分枝杆菌的近亲，在感染过程中，它在细菌表面聚合宿主肌动蛋白，以驱动细胞内运动和细胞间传播。然而，夺取肌动蛋白聚合的分枝杆菌因子仍然是难以捉摸的。在这里，我们报道了M. marinum肌动蛋白为基础的运动因子的鉴定和表征，称为分枝杆菌胞内火箭A (MirA)，这是一个富含甘氨酸的PE_PGRS蛋白家族的成员。MirA含有一个两亲螺旋，可以锚定在分枝杆菌的外膜上，令人惊讶的是，它也可以锚定在宿主脂滴细胞器的表面。MirA直接结合并激活宿主蛋白N-WASP，通过Arp2/3复合物刺激肌动蛋白聚合，指导细菌和脂滴基于肌动蛋白的运动。MirA不同于已知的N-WASP激活配体，可能代表了一类新的微生物和宿主肌动蛋白调节剂。此外，MirA-N-WASP相互作用为理解神秘的PE_PGRS蛋白如何促进分枝杆菌发病提供了一个模型。海洋分枝杆菌是结核分枝杆菌的近亲，在感染过程中，在细菌表面聚合宿主肌动蛋白以驱动细胞内运动和细胞间传播。在这里，Hill & Welch发现了一种海洋分枝杆菌表面蛋白，该蛋白结合并激活宿主蛋白NWASP，以刺激肌动蛋白聚合并驱动细菌基于肌动蛋白的运动。
Many key insights into actin regulation have been derived through examining how microbial pathogens intercept the actin cytoskeleton during infection. Mycobacterium marinum, a close relative of the human pathogen Mycobacterium tuberculosis, polymerizes host actin at the bacterial surface to drive intracellular movement and cell-to-cell spread during infection. However, the mycobacterial factor that commandeers actin polymerization has remained elusive. Here, we report the identification and characterization of the M. marinum actin-based motility factor designated mycobacterial intracellular rockets A (MirA), which is a member of the glycine-rich PE_PGRS protein family. MirA contains an amphipathic helix to anchor into the mycobacterial outer membrane and, surprisingly, also the surface of host lipid droplet organelles. MirA directly binds to and activates the host protein N-WASP to stimulate actin polymerization through the Arp2/3 complex, directing both bacterial and lipid droplet actin-based motility. MirA is dissimilar to known N-WASP activating ligands and may represent a new class of microbial and host actin regulator. Additionally, the MirA-N-WASP interaction represents a model to understand how the enigmatic PE_PGRS proteins contribute to mycobacterial pathogenesis. Mycobacterium marinum, a close relative of Mycobacterium tuberculosis, polymerizes host actin at the bacterial surface to drive intracellular movement and cell-to-cell spread during infection. Here, Hill & Welch identify an M. marinum surface protein that binds to and activates the host protein NWASP to stimulate actin polymerization and drive bacterial actin-based motility.
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