9QQW

EM structure of Rec-controlled histidine kinase LvrB, BeF3-activated

Summary for 9QQW

• Entry DOI: 10.2210/pdb9qqw/pdb
• EMDB information: 53315
• Descriptor: histidine kinase, MAGNESIUM ION, BERYLLIUM TRIFLUORIDE ION, ... (5 entities in total)
• Functional Keywords: histidine kinase, signaling protein
• Biological source: Leptospira interrogans serovar Copenhageni
• Total number of polymer chains: 2
• Total formula weight: 87485.26

Authors

Agustoni, E.,Mechaly, A.,Rizza, J.D.,Beriashvili, D.,Pluhackova, K.,Isaikina, P.,Trajtenberg, F.,Muntener, T.,Wunder, E.,Ko, A.,Schirmer, T.,Buschiazzo, A.,Hiller, S. (deposition date: 2025-04-02, release date: 2026-04-15, Last modification date: 2026-10-07)

Primary citation

Agustoni, E.,Mechaly, A.,Dalla Rizza, J.,Beriashvili, D.,Pluhackova, K.,Isaikina, P.,Trajtenberg, F.,Muntener, T.,Wunder Jr., E.A.,Ko, A.I.,Schirmer, T.,Buschiazzo, A.,Hiller, S.
Activation mechanism of the full-length histidine kinase LvrB from pathogenic Leptospira.
Nat Commun, 17:-, 2026

PubMed 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.

PubMed: 41991510
DOI: 10.1038/s41467-026-71783-4

Experimental method

ELECTRON MICROSCOPY (5.92 Å)