Structural Insight into the Role of the PAS Domain for Signal Transduction in Sensor Kinase BvgS

Elian Dupré, Bernard Clantin, Youhua Yuan, Sophie Lecher, Elodie Lesne, Rudy Antoine, Vincent Villeret, Françoise Jacob-Dubuisson*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

The two-component system BvgAS controls the virulence regulon in Bordetella pertussis. BvgS is the prototype of a family of sensor histidine kinases harboring periplasmic Venus flytrap (VFT) domains. The VFT domains are connected to the cytoplasmic kinase moiety by helical linkers separated by a Per-ARNT-Sim (PAS) domain. Antagonism between the two linkers, as one forms a coiled coil when the other is dynamic and vice versa, regulates BvgS activity. Here, we solved the structure of the intervening PAS domain by X-ray crystallography. Two forms were obtained that notably differ by the connections between the PAS core domain and the flanking helical linkers. Structure-guided mutagenesis indicated that those connections participate in the regulation of BvgS activity. Thus, the PAS domain appears to function as a switch facilitator module whose conformation determines the output of the system. As many BvgS homologs have similar architectures, the mechanisms unveiled here are likely to generally apply to the regulation of sensor histidine kinases of that family.

Original languageEnglish
Article numbere00614
JournalJournal of Bacteriology
Volume203
Issue number9
DOIs
Publication statusPublished - May 2021

Bibliographical note

Funding Information:
We thank Hugo Bidois for the first mutations and β-gal analyses. This work was initiated with grant ANR-13-BSV8-0002-01 to F.J.-D. and then pursued with the financial support of Inserm and the University of Lille. Y. Yuan acknowledges financial support from the Henan Provincial Hospital. The funders had no role in designing the experiments or analyzing the data.

Publisher Copyright:
© 2021 American Society for Microbiology. All Rights Reserved.

Keywords

  • Bordetella pertussis
  • Pas domain
  • Sensor kinases
  • Two-component system
  • Virulence regulation

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