Activation mechanism of the full-length histidine kinase LvrB from pathogenic Leptospira

Pathogenic Leptospira modulate their virulence via the Lvr signaling system, with the histidine kinase LvrB being a central element. LvrB is a prototype of Rec-controlled histidine kinases, which are frequently found in bacterial two-component systems, and yet whose regulatory mechanisms remain largely unknown. Here, we report full-length structures of LvrB in different states uncovering its mechanism of activation. Kinase-inactive LvrB is a symmetric homodimer, with its catalytic domains rigidly clasped onto the central helical domain. Phosphorylation of the N-terminal Rec domains induces coiled-coil formation of the central αS helices thereby breaking symmetry through liberation of the catalytic domains into a dynamic, auto-phosphorylation competent state. We further identified LvrB's downstream effector partner LvrC, an anti-σ factor that reprograms the transcription of hundreds of virulence genes. Our findings set a mechanistic paradigm for Rec-controlled histidine kinases enabling the design of virulence inhibitors.

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Journal
Nature Communications
Published
2026-04-16
DOI
https://doi.org/10.1038/s41467-026-71783-4
Primary Topic
Leptospirosis research and findings
Type
article
Field-Weighted Citation Impact
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article

Activation mechanism of the full-length histidine kinase LvrB from pathogenic Leptospira

Tilman Schirmer, Elsio A. Wunder, Ariel Méchaly, Kristýna Pluháčková et al.
Nature Communications
Leptospirosis research and findings
article

Activation mechanism of the full-length histidine kinase LvrB from pathogenic Leptospira

Tilman Schirmer, Elsio A. Wunder, Ariel Méchaly, Kristýna Pluháčková, Albert Icksang Ko, Joaquín Dalla Rizza, Thomas Müntener, Felipe Trajtenberg, David Beriashvili, Sebastian Hiller, Polina Isaikina, Elia Agustoni, Alejandro Buschiazzo
article en

Abstract

Pathogenic Leptospira modulate their virulence via the Lvr signaling system, with the histidine kinase LvrB being a central element. LvrB is a prototype of Rec-controlled histidine kinases, which are frequently found in bacterial two-component systems, and yet whose regulatory mechanisms remain largely unknown. Here, we report full-length structures of LvrB in different states uncovering its mechanism of activation. Kinase-inactive LvrB is a symmetric homodimer, with its catalytic domains rigidly clasped onto the central helical domain. Phosphorylation of the N-terminal Rec domains induces coiled-coil formation of the central αS helices thereby breaking symmetry through liberation of the catalytic domains into a dynamic, auto-phosphorylation competent state. We further identified LvrB's downstream effector partner LvrC, an anti-σ factor that reprograms the transcription of hundreds of virulence genes. Our findings set a mechanistic paradigm for Rec-controlled histidine kinases enabling the design of virulence inhibitors.

Nature Communications
University of Stuttgart (DE), University of Connecticut (US), Institut Pasteur (FR), University of Basel (CH), Paul Scherrer Institute (CH), Yale University (US), Institut Pasteur de Montevideo (UY), Fundação Oswaldo Cruz (BR)
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
Openalex Percentile: Top 20%
Leptospirosis research and findings
DOIOpen Access PDFOpenAlex
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