4Q0C

3.1 A resolution crystal structure of the B. pertussis BvgS periplasmic domain

Summary for 4Q0C

• Entry DOI: 10.2210/pdb4q0c/pdb
• Descriptor: Virulence sensor protein BvgS (1 entity in total)
• Functional Keywords: bacterial extracellular solute-binding proteins, family 3, venus fly trap, periplasmic binding protein, sensor domain, virulence regulation, environmental signals, signal perception, transferase
• Biological source: Bordetella pertussis
• Cellular location: Cell inner membrane ; Multi- pass membrane protein : P16575
• Total number of polymer chains: 4
• Total formula weight: 256420.45

Authors

Dupre, E.,Herrou, J.,Lensink, M.F.,Wintjens, R.,Lebedev, A.,Crosson, S.,Villeret, V.,Locht, C.,Antoine, R.,Jacob-Dubuisson, F. (deposition date: 2014-04-01, release date: 2015-02-11, Last modification date: 2023-09-20)

Primary citation

Dupre, E.,Herrou, J.,Lensink, M.F.,Wintjens, R.,Vagin, A.,Lebedev, A.,Crosson, S.,Villeret, V.,Locht, C.,Antoine, R.,Jacob-Dubuisson, F.
Virulence Regulation with Venus Flytrap Domains: Structure and Function of the Periplasmic Moiety of the Sensor-Kinase BvgS.
Plos Pathog., 11:e1004700-e1004700, 2015

PubMed Abstract: 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.

PubMed: 25738876
DOI: 10.1371/journal.ppat.1004700

Experimental method

X-RAY DIFFRACTION (3.1 Å)