Virulence regulation with Venus flytrap ...
Type de document :
Article dans une revue scientifique
PMID :
URL permanente :
Titre :
Virulence regulation with Venus flytrap domains: structure and function of the periplasmic moiety of the sensor-kinase BvgS
Auteur(s) :
Dupré, Elian [Auteur]
Herrou, Julien [Auteur]
Lensink, Marc [Auteur]
Wintjens, René [Auteur]
Vagin, Alexey [Auteur]
Lebedev, Andrey [Auteur]
Crosson, Sean [Auteur]
Villeret, Vincent [Auteur]
Locht, Camille [Auteur]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Antoine, Rudy [Auteur]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Jacob-Dubuisson, Françoise [Auteur]
Herrou, Julien [Auteur]
Lensink, Marc [Auteur]
Wintjens, René [Auteur]
Vagin, Alexey [Auteur]
Lebedev, Andrey [Auteur]
Crosson, Sean [Auteur]
Villeret, Vincent [Auteur]
Locht, Camille [Auteur]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Antoine, Rudy [Auteur]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Jacob-Dubuisson, Françoise [Auteur]
Titre de la revue :
PLoS Pathogens
Nom court de la revue :
PLoS Pathog.
Numéro :
11
Pagination :
e1004700
Date de publication :
2015-03
ISSN :
1553-7374
Mot(s)-clé(s) en anglais :
Droseraceae
Signal Transduction
X-ray Crystallography
Site-directed mutagenesis
Virulence
Models, Molecular
Periplasm
Transcription Factors
Bordetella pertussis
Bacterial Proteins
Signal Transduction
X-ray Crystallography
Site-directed mutagenesis
Virulence
Models, Molecular
Periplasm
Transcription Factors
Bordetella pertussis
Bacterial Proteins
Discipline(s) HAL :
Chimie/Chimie théorique et/ou physique
Résumé en anglais : [en]
Two-component systems (TCS) represent major signal-transduction pathways for adaptation to environmental conditions, and regulate many aspects of bacterial physiology. In the whooping cough agent Bordetella pertussis, the ...
Lire la suite >Two-component systems (TCS) represent major signal-transduction pathways for adaptation to environmental conditions, and regulate many aspects of bacterial physiology. In the whooping cough agent Bordetella pertussis, the TCS BvgAS controls the virulence regulon, and is therefore critical for pathogenicity. BvgS is a prototypical TCS sensor-kinase with tandem periplasmic Venus flytrap (VFT) domains. VFT are bi-lobed domains that typically close around specific ligands using clamshell motions. We report the X-ray structure of the periplasmic moiety of BvgS, an intricate homodimer with a novel architecture. By combining site-directed mutagenesis, functional analyses and molecular modeling, we show that the conformation of the periplasmic moiety determines the state of BvgS activity. The intertwined structure of the periplasmic portion and the different conformation and dynamics of its mobile, membrane-distal VFT1 domains, and closed, membrane-proximal VFT2 domains, exert a conformational strain onto the transmembrane helices, which sets the cytoplasmic moiety in a kinase-on state by default corresponding to the virulent phase of the bacterium. Signaling the presence of negative signals perceived by the periplasmic domains implies a shift of BvgS to a distinct state of conformation and activity, corresponding to the avirulent phase. The response to negative modulation depends on the integrity of the periplasmic dimer, indicating that the shift to the kinase-off state implies a concerted conformational transition. This work lays the bases to understand virulence regulation in Bordetella. As homologous sensor-kinases control virulence features of diverse bacterial pathogens, the BvgS structure and mechanism may pave the way for new modes of targeted therapeutic interventions.Lire moins >
Lire la suite >Two-component systems (TCS) represent major signal-transduction pathways for adaptation to environmental conditions, and regulate many aspects of bacterial physiology. In the whooping cough agent Bordetella pertussis, the TCS BvgAS controls the virulence regulon, and is therefore critical for pathogenicity. BvgS is a prototypical TCS sensor-kinase with tandem periplasmic Venus flytrap (VFT) domains. VFT are bi-lobed domains that typically close around specific ligands using clamshell motions. We report the X-ray structure of the periplasmic moiety of BvgS, an intricate homodimer with a novel architecture. By combining site-directed mutagenesis, functional analyses and molecular modeling, we show that the conformation of the periplasmic moiety determines the state of BvgS activity. The intertwined structure of the periplasmic portion and the different conformation and dynamics of its mobile, membrane-distal VFT1 domains, and closed, membrane-proximal VFT2 domains, exert a conformational strain onto the transmembrane helices, which sets the cytoplasmic moiety in a kinase-on state by default corresponding to the virulent phase of the bacterium. Signaling the presence of negative signals perceived by the periplasmic domains implies a shift of BvgS to a distinct state of conformation and activity, corresponding to the avirulent phase. The response to negative modulation depends on the integrity of the periplasmic dimer, indicating that the shift to the kinase-off state implies a concerted conformational transition. This work lays the bases to understand virulence regulation in Bordetella. As homologous sensor-kinases control virulence features of diverse bacterial pathogens, the BvgS structure and mechanism may pave the way for new modes of targeted therapeutic interventions.Lire moins >
Langue :
Anglais
Audience :
Non spécifiée
Établissement(s) :
CHU Lille
CNRS
Inserm
Université de Lille
Institut Pasteur de Lille
CNRS
Inserm
Université de Lille
Institut Pasteur de Lille
Équipe(s) de recherche :
Computational Molecular Systems Biology
Biologie structurale et intégrative
Biologie structurale et intégrative
Date de dépôt :
2020-02-12T15:11:16Z
2021-05-12T07:02:53Z
2021-05-12T07:02:53Z