Link to Pubmed [PMID] – 32720355
Link to DOI – 10.1111/cmi.13246
Cell. Microbiol. 2020 Jul; (): e13246
Intracellular bacterial pathogens harbor genes, the closest homologues of which are found in eukaryotes. Regulator of chormosome 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, harbor RCC1 repeat coding genes. L. 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 stabilization, pathogen vacuole motility and intracellular bacterial growth as well as host cell migration. The RCC1 repeat effectors localize 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. C. burnetii translocates the RCC1 repeat effector NopA into host cells, where the effector localizes 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 signaling. 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 This article is protected by copyright. All rights reserved.