Brucella effectors NyxA and NyxB target SENP3 to modulate the subcellular localisation of nucleolar proteins.

Autor: Louche A; Laboratory of Molecular Microbiology and Structural Biochemistry, Centre National de la Recherche Scientifique UMR5086, Université de Lyon, Lyon, France., Blanco A; Laboratory of Molecular Microbiology and Structural Biochemistry, Centre National de la Recherche Scientifique UMR5086, Université de Lyon, Lyon, France., Lacerda TLS; Laboratory of Molecular Microbiology and Structural Biochemistry, Centre National de la Recherche Scientifique UMR5086, Université de Lyon, Lyon, France., Cancade-Veyre L; Laboratory of Molecular Microbiology and Structural Biochemistry, Centre National de la Recherche Scientifique UMR5086, Université de Lyon, Lyon, France., Lionnet C; Laboratoire de Reproduction et Développement des Plantes, Université de Lyon, ENS de Lyon, UCBL, INRA, CNRS, Lyon, France., Bergé C; Laboratory of Molecular Microbiology and Structural Biochemistry, Centre National de la Recherche Scientifique UMR5086, Université de Lyon, Lyon, France., Rolando M; Institut Pasteur, Université Paris Cité, Biologie des Bactéries Intracellulaires, CNRS UMR 6047, Paris, France., Lembo F; Aix-Marseille Université, Inserm, Institut Paoli-Calmettes, CNRS, Centre de Recherche en Cancérologie de Marseille (CRCM), Marseille, France., Borg JP; Aix-Marseille Université, Inserm, Institut Paoli-Calmettes, CNRS, Centre de Recherche en Cancérologie de Marseille (CRCM), Marseille, France.; Institut Universitaire de France, Paris, France., Buchrieser C; Institut Pasteur, Université Paris Cité, Biologie des Bactéries Intracellulaires, CNRS UMR 6047, Paris, France., Nagahama M; Laboratory of Molecular and Cellular Biochemistry, Meiji Pharmaceutical University, Tokyo, Japan., Gérard FCA; Laboratory of Molecular Microbiology and Structural Biochemistry, Centre National de la Recherche Scientifique UMR5086, Université de Lyon, Lyon, France., Gorvel JP; Aix-Marseille Univ, CNRS, INSERM, CIML, Marseille, France., Gueguen-Chaignon V; Protein Science Facility, SFR Biosciences, Centre National de la Recherche Scientifique UAR3444, INSERM US8, Université de Lyon, ENS de Lyon, Lyon, France., Terradot L; Laboratory of Molecular Microbiology and Structural Biochemistry, Centre National de la Recherche Scientifique UMR5086, Université de Lyon, Lyon, France. laurent.terradot@ibcp.fr., Salcedo SP; Laboratory of Molecular Microbiology and Structural Biochemistry, Centre National de la Recherche Scientifique UMR5086, Université de Lyon, Lyon, France. suzana.salcedo@ibcp.fr.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2023 Jan 06; Vol. 14 (1), pp. 102. Date of Electronic Publication: 2023 Jan 06.
DOI: 10.1038/s41467-022-35763-8
Abstrakt: The cell nucleus is a primary target for intracellular bacterial pathogens to counteract immune responses and hijack host signalling pathways to cause disease. Here we identify two Brucella abortus effectors, NyxA and NyxB, that interfere with host protease SENP3, and this facilitates intracellular replication of the pathogen. The translocated Nyx effectors directly interact with SENP3 via a defined acidic patch (identified from the crystal structure of NyxB), preventing nucleolar localisation of SENP3 at late stages of infection. By sequestering SENP3, the effectors promote cytoplasmic accumulation of nucleolar AAA-ATPase NVL and ribosomal protein L5 (RPL5) in effector-enriched structures in the vicinity of replicating bacteria. The shuttling of ribosomal biogenesis-associated nucleolar proteins is inhibited by SENP3 and requires the autophagy-initiation protein Beclin1 and the SUMO-E3 ligase PIAS3. Our results highlight a nucleomodulatory function of two Brucella effectors and reveal that SENP3 is a crucial regulator of the subcellular localisation of nucleolar proteins during Brucella infection, promoting intracellular replication of the pathogen.
(© 2023. The Author(s).)
Databáze: MEDLINE
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