Divergent Evolution of Legionella RCC1 Repeat Effectors Defines the Range of Ran GTPase Cycle Targets
In: ISSN: 2161-2129, 2020
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International audience ; Legionella pneumophila governs its interactions with host cells by secreting >300 different "effector" proteins. Some of these effectors contain eukaryotic domains such as the RCC1 (regulator of chromosome condensation 1) repeats promoting the activation of the small GTPase Ran. In this report, we reveal a conserved pattern of L. pneumophila RCC1 repeat genes, which are distributed in two main clusters of strains. Accordingly, strain Philadelphia-1 contains two RCC1 genes implicated in bacterial virulence, legG1 (Legionella eukaryotic gene 1), and ppgA, while strain Paris contains only one, pieG. The RCC1 repeat effectors localize to different cellular compartments and bind distinct components of the Ran GTPase cycle, including Ran modulators and the small GTPase itself, and yet they all promote the activation of Ran. The pieG gene spans the corresponding open reading frames of legG1 and a separate adjacent upstream gene, lpg1975. legG1 and lpg1975 are fused upon addition of a single nucleotide to encode a protein that adopts the binding specificity of PieG. Thus, a point mutation in pieG splits the gene, altering the effec-tor target. These results indicate that divergent evolution of RCC1 repeat effectors defines the Ran GTPase cycle targets and that modulation of different components of the cycle might fine-tune Ran activation during Legionella infection.IMPORTANCE Legionella pneumophila is a ubiquitous environmental bacterium which, upon inhalation, causes a life-threatening pneumonia termed Legionnaires' disease. The opportunistic pathogen grows in amoebae and macrophages by employing a "type IV" secretion system, which secretes more than 300 different "effec-tor" proteins into the host cell, where they subvert pivotal processes. The function of many of these effector proteins is unknown, and their evolution has not been studied. L. pneumophila RCC1 repeat effectors target the small GTPase Ran, a molecular switch implicated in different cellular processes such as ...
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Divergent Evolution of Legionella RCC1 Repeat Effectors Defines the Range of Ran GTPase Cycle Targets
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| Autor/in / Beteiligte Person: | Swart, A. Leoni ; Steiner, Bernhard ; Gomez-Valero, Laura ; Schütz, Sabina ; Hannemann, Mandy ; Janning, Petra ; Irminger, Michael ; Rothmeier, Eva ; Buchrieser, Carmen ; Itzen, Aymelt ; Panse, Vikram ; Hilbi, Hubert ; Institute of Medical Microbiology Zurich ; Universität Zürich Zürich (UZH) ; Biologie des Bactéries intracellulaires - Biology of Intracellular Bacteria ; Institut Pasteur Paris -Centre National de la Recherche Scientifique (CNRS) ; Center for Integrated Protein Science (CIPSM) ; Technical University of Munich (TUM)-Ludwig Maximilian University of Munich Germany (LMU München)-Helmholtz-Zentrum München (HZM) ; Max-Planck-Institut für Molekulare Physiologie ; Max-Planck-Gesellschaft ; Max Von Pettenkofer Institute (MVP) ; Ludwig-Maximilians-Universität München (LMU) ; Institute of Biochemistry and Signal Transduction Hamburg, Germany ; Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf Hamburg (UKE) ; Research in the laboratory of H.H. was supported by the Swiss National Science Foundation (SNF ; 31003A_153200 and 31003A_175557), the OPO Foundation, and the Novartis Foundation for Medical-Biological Research. A. Welin was supported by a grant from the Swedish Research Council (2014-396). V.G.P. was supported by grants from the Swiss National Science Foundation, NCCR RNA & Disease, Novartis Foundation for Medical-Biological Research and the Olga Mayenfisch Foundation. ; Work in the laboratory of C.B. was financed by the Institut Pasteur and by grant ANR-10-LABX-62-IBEID. ; We thank Amanda Welin for performing imaging flow cytometry experiments and Nadia Keller for flow cytometry analysis. ; Confocal laser scanning microscopy and imaging flow cytometry were performed using equipment of the Center of Microscopy and Image Analysis, University of Zurich. Proteomics analysis was performed at the Functional Genomics Center Zürich. ; ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010) |
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| Zeitschrift: | ISSN: 2161-2129, 2020 |
| Veröffentlichung: | HAL CCSD ; American Society for Microbiology, 2020 |
| Medientyp: | academicJournal |
| DOI: | 10.1128/mBio.00405-20 |
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