The unique Brucella effectors NyxA and NyxB target SENP3 to modulate the subcellular localisation of nucleolar proteins
| Autor: | Jean-Paul Borg, Bergé C, Gueguen-Chaignon, Blanco A, Lacerda Tls, Lionnet C, Frédérique Lembo, Suzana P. Salcedo, Buchrieser C, Nagahama M, Arthur Louche, Laurent Terradot, Rolando M, Jean-Pierre Gorvel |
|---|---|
| Přispěvatelé: | Microbiologie moléculaire et biochimie structurale / Molecular Microbiology and Structural Biochemistry (MMSB), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0303 health sciences
education.field_of_study Effector Protein subunit [SDV]Life Sciences [q-bio] 030302 biochemistry & molecular biology Context (language use) Biology 3. Good health Ribosomal protein L5 Cell biology 03 medical and health sciences Cell nucleus medicine.anatomical_structure medicine Nuclear protein Receptor education Intracellular 030304 developmental biology |
| Popis: | The cell nucleus is a primary target for intracellular bacterial pathogens to counteract immune responses and hijack host signalling pathways to cause disease. The mechanisms controlling nuclear protein localisation in the context of stress responses induced upon bacterial infection are still poorly understood. Here we show that theBrucella abortuseffectors NyxA and NyxB interfere with the host sentrin specific protease 3 (SENP3), which is essential for intracellular replication. Translocated Nyx effectors directly interact with SENP3viaa defined acidic patch identified from the crystal structure of NyxB, preventing its nucleolar localisation at the late stages of the infection. By sequestering SENP3, the Nyx effectors induce the cytoplasmic accumulation of the nucleolar AAA-ATPase NVL, the large subunit ribosomal protein L5 (RPL5) and the ribophagy receptor NUFIP1 in Nyx-enriched structures in the vicinity of replicating bacteria. This shuttling of ribosomal biogenesis-associated nucleolar proteins is negatively regulated by SENP3 and dependent on the autophagy-initiation protein Beclin1, indicative of a ribophagy-derived process induced duringBrucellainfection. Our results highlight a new nucleomodulatory function by two uniqueBrucellaeffectors, and reveal that SENP3 is a critical regulator of the subcellular localisation of multiple nucleolar proteins duringBrucellainfection, promoting intracellular replication. |
| Databáze: | OpenAIRE |
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