Intracellular bacterial pathogens harbour genes, the closest homologues of which are found in eukaryotes. Regulator of chromosome condensation 1 (RCC1) repeat proteins are phylogenetically widespread and implicated in protein–protein interactions, such as the activation of the small GTPase Ran by its cognate guanine nucleotide exchange factor, RCC1. Legionella pneumophila and Coxiella burnetii, the causative agents of Legionnaires' disease and Q fever, respectively, harbour RCC1 repeat coding genes. Legionella pneumophila secretes the RCC1 repeat ‘effector’ proteins LegG1, PpgA and PieG into eukaryotic host cells, where they promote the activation of the pleiotropic small GTPase Ran, microtubule stabilisation, pathogen vacuole motility and intracellular bacterial growth as well as host cell migration. The RCC1 repeat effectors localise to the pathogen vacuole or the host plasma membrane and target distinct components of the Ran GTPase cycle, including Ran modulators and the small GTPase itself. Coxiella burnetii translocates the RCC1 repeat effector NopA into host cells, where the protein localises to nucleoli. NopA binds to Ran GTPase and promotes the nuclear accumulation of Ran(GTP), thus pertubing the import of the transcription factor NF‐κB and innate immune signalling. Hence, divergent evolution of bacterial RCC1 repeat effectors defines the range of Ran GTPase cycle targets and likely allows fine‐tuning of Ran GTPase activation by the pathogens at different cellular sites.

中文翻译：

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细菌 RCC1 重复效应子的进化和功能。

细胞内细菌病原体含有基因，在真核生物中发现了其最接近的同源物。染色体浓缩调节因子 1 (RCC1) 重复蛋白在系统发育上广泛存在并涉及蛋白质-蛋白质相互作用，例如通过其同源鸟嘌呤核苷酸交换因子 RCC1 激活小 GTPase Ran。Legionella pneumophila和Coxiellaburnetii分别是军团病和 Q 热的病原体，它们含有 RCC1 重复编码基因。嗜肺军团菌将 RCC1 重复“效应子”蛋白 LegG1、PpgA 和 PieG 分泌到真核宿主细胞中，在那里它们促进多效性小 GTPase Ran 的激活、微管稳定、病原体液泡运动和细胞内细菌生长以及宿主细胞迁移。RCC1 重复效应子定位于病原体液泡或宿主质膜，并靶向 Ran GTPase 循环的不同组分，包括 Ran 调节剂和小 GTPase 本身。伯尼氏杆菌将 RCC1 重复效应子 NopA 转移到宿主细胞中，在那里蛋白质定位于核仁。NopA 与 Ran GTPase 结合并促进 Ran (GTP) 的核积累，从而干扰转录因子 NF-κB 的输入和先天免疫信号。因此，细菌 RCC1 重复效应子的不同进化定义了 Ran GTPase 循环目标的范围，并可能允许不同细胞位点的病原体对 Ran GTPase 的激活进行微调。