8VC9

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

Summary for 8VC9

• Entry DOI: 10.2210/pdb8vc9/pdb
• Descriptor: Leptospira virulence regulator B (LvrB), PHOSPHOMETHYLPHOSPHONIC ACID ADENYLATE ESTER, MAGNESIUM ION, ... (6 entities in total)
• Functional Keywords: two component systems, hybrid response regulator, seudo-phosphorylated form, signaling protein
• Biological source: Leptospira interrogans serovar Copenhageni
• Total number of polymer chains: 6
• Total formula weight: 264662.60

Authors

Mechaly, A.,Buschiazzo, A. (deposition date: 2023-12-13, release date: 2024-12-18, Last modification date: 2026-07-01)

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

X-RAY DIFFRACTION (2.65 Å)