Coiled-Coil Antagonism Regulates Activity of Venus Flytrap-Domain-Containing Sensor Kinases of the BvgS Family
| Autor: | Lesne, Elodie, Dupré, Elian, Lensink, Marc, Locht, Camille, Antoine, Rudy, Jacob-Dubuisson, Françoise |
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| Přispěvatelé: | Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 (UGSF), Institut National de la Recherche Agronomique (INRA)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), E.L. received a doctoral fellowship from the Region Nord-Pas-de-Calais and INSERM. This work was supported by the Agence Nationale de la Recherche (grant number ANR-13-BSV8-0002-01 to F.J.-D.)., We thank Eva-Maria Krammer for her initial modeling work., ANR-13-BSV8-0002,MECA VENUS,Mécanismes moléculaires de la transduction de signal par BvgS, un modèle de la famille de récepteurs kinases bactériens à domaines Vénus Flytrap(2013), Centre d’Infection et d’Immunité de Lille (CIIL) - U1019 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA), Jacob-Dubuisson, Françoise, Blanc 2013 - Mécanismes moléculaires de la transduction de signal par BvgS, un modèle de la famille de récepteurs kinases bactériens à domaines Vénus Flytrap - - MECA VENUS2013 - ANR-13-BSV8-0002 - Blanc 2013 - VALID, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Université de Lille-Centre National de la Recherche Scientifique (CNRS) |
| Rok vydání: | 2018 |
| Předmět: |
MESH: Transcription Factors/metabolism
MESH: Transcription Factors/chemistry sensor kinases coiled coil Protein Conformation two-component regulatory systems [SDV]Life Sciences [q-bio] Molecular Dynamics Simulation BvgS family Microbiology QR1-502 MESH: Bacterial Proteins/metabolism Bordetella pertussis [SDV] Life Sciences [q-bio] MESH: Protein Conformation Bacterial Proteins MESH: Bacterial Proteins/chemistry MESH: Molecular Dynamics Simulation Transcription Factors Research Article |
| Zdroj: | mBio mBio, American Society for Microbiology, 2018, 9 (1), pp.e02052-17. ⟨10.1128/mBio.02052-17⟩ mBio, 2018, 9 (1), pp.e02052-17. ⟨10.1128/mBio.02052-17⟩ mBio, Vol 9, Iss 1 (2018) |
| ISSN: | 2150-7511 2161-2129 |
| DOI: | 10.1128/mBio.02052-17⟩ |
| Popis: | Bordetella pertussis controls the expression of its virulence regulon through the two-component system BvgAS. BvgS is a prototype for a family of multidomain sensor kinases. In BvgS, helical linkers connect periplasmic Venus flytrap (VFT) perception domains to a cytoplasmic Per-Arnt-Sim (PAS) domain and the PAS domain to the dimerization/histidine phosphotransfer (DHp) domain of the kinase. The two linkers can adopt coiled-coil structures but cannot do so simultaneously. The first linker forms a coiled coil in the kinase mode and the second in the phosphatase mode, with the other linker in both cases showing an increase in dynamic behavior. The intervening PAS domain changes its quaternary structure between the two modes. In BvgS homologues without a PAS domain, a helical “X” linker directly connects the VFT and DHp domains. Here, we used BvgS as a platform to characterize regulation in members of the PAS-less subfamily. BvgS chimeras of homologues with natural X linkers displayed various regulation phenotypes. We identified two distinct coiled-coil registers in the N- and C-terminal portions of the X linkers. Stable coil formation in the C-terminal moiety determines the phosphatase mode, similarly to BvgS; in contrast, coil formation in the N-terminal moiety along the other register leads to the kinase mode. Thus, antagonism between two registers in the VFT-DHp linker forms the basis for activity regulation in the absence of the PAS domain. The N and C moieties of the X linker play roles similar to those played by the two independent linkers in sensor kinases with a PAS domain, providing a unified mechanism of regulation for the entire family. IMPORTANCE The whooping cough agent Bordetella pertussis uses the BvgAS sensory transduction two-component system to regulate production of its virulence factors. BvgS serves as a model for a large family of multidomain bacterial sensor kinases. B. pertussis is virulent when BvgS functions as a kinase and avirulent when it switches to phosphatase activity in response to modulating signals. Understanding the molecular regulation of those proteins might lead to new antibacterial strategies. Here, we show that the linker regions between the perception and the enzymatic domains shift between distinct states of conformation in an alternating manner in response to signals and that their antagonistic changes control sensor kinase activity. These linker regions and mechanistic principles appear to be conserved among BvgS homologues, irrespective of the presence or absence of an intervening domain between the perception and the enzymatic domains. This work has thus uncovered general molecular mechanisms that regulate activity of sensor kinases in the BvgS family. |
| Databáze: | OpenAIRE |
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