Virulence regulation with Venus flytrap domains: structure and function of the periplasmic moiety of the sensor-kinase BvgS

PLoS Pathogens
Elian DupréF Jacob-Dubuisson

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...Continue Reading

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Citations

Feb 6, 2017·Pathogens and Disease·Yukihiro HiramatsuKazunari Kamachi
Jul 5, 2017·Journal of Bacteriology·Hrishiraj SenPeter A Lund
May 17, 2017·Journal of Bacteriology·Elodie LesneFrançoise Jacob-Dubuisson
Sep 23, 2016·Clinical and Vaccine Immunology : CVI·Nicholas H CarbonettiMaria E Rodriguez
Oct 12, 2017·MBio·Kyung MoonDeborah M Hinton
Jul 17, 2018·Nature Reviews. Microbiology·Françoise Jacob-DubuissonRudy Antoine
Feb 9, 2017·Proceedings of the National Academy of Sciences of the United States of America·M Ashley BoneSteven M Julio
Dec 28, 2017·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Ivan Gushchin, Valentin Gordeliy
Feb 24, 2021·Journal of Bacteriology·Elian DupréFrançoise Jacob-Dubuisson
Apr 1, 2016·Clinical Microbiology Reviews·Paul E KilgoreHeinz-Josef Schmitt

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Methods Mentioned

BETA
X-ray
PCR
PISA

Software Mentioned

refine
Coot
MOLREP
Modeller
Phenix
REFMAC
XDS

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