Department of Respiratory Medicine, Center for Pathogen Biology and Infectious Diseases, Key Laboratory of Organ Regeneration and Transplantation of the Ministry of Education, State Key Laboratory for Zoonotic Diseases, The First Hospital of Jilin University, Changchun, China.
Department of Microbiology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
Elife. 2022 Feb 17;11:e73220. doi: 10.7554/eLife.73220.
The cytoskeleton network of eukaryotic cells is essential for diverse cellular processes, including vesicle trafficking, cell motility, and immunity, thus is a common target for bacterial virulence factors. A number of effectors from the bacterial pathogen have been shown to modulate the function of host actin cytoskeleton to construct the -containing vacuole (LCV) permissive for its intracellular replication. In this study, we found that the Dot/Icm effector Lem8 (Lpg1290) is a protease whose activity is catalyzed by a Cys-His-Asp motif known to be associated with diverse biochemical activities. Intriguingly, we found that Lem8 interacts with the host regulatory protein 14-3-3ζ, which activates its protease activity. Furthermore, Lem8 undergoes self-cleavage in a process that requires 14-3-3ζ. We identified the Pleckstrin homology-like domain-containing protein Phldb2 involved in cytoskeleton organization as a target of Lem8 and demonstrated that Lem8 plays a role in the inhibition of host cell migration by attacking Phldb2.
真核细胞的细胞骨架网络对于包括囊泡运输、细胞运动和免疫在内的多种细胞过程至关重要，因此是细菌毒力因子的共同靶标。已经证明，来自细菌病原体的许多效应物可以调节宿主肌动蛋白细胞骨架的功能，以构建容纳其细胞内复制的含有（LCV）。在这项研究中，我们发现 Dot/Icm 效应物 Lem8（Lpg1290）是一种蛋白酶，其活性由与多种生化活性相关的 Cys-His-Asp 基序催化。有趣的是，我们发现 Lem8 与宿主调节蛋白 14-3-3ζ 相互作用，后者激活其蛋白酶活性。此外，Lem8 在需要 14-3-3ζ 的过程中发生自我切割。我们确定了参与细胞骨架组织的含有 Pleckstrin 同源结构域的蛋白 Phldb2 是 Lem8 的靶标，并证明 Lem8 通过攻击 Phldb2 来抑制宿主细胞迁移中发挥作用。
