9P6I

Crystal Structure of the Histidine Kinase VC2136 from Vibrio cholerae serotype O1

Summary for 9P6I

• Entry DOI: 10.2210/pdb9p6i/pdb
• Descriptor: histidine kinase, SULFATE ION, CHLORIDE ION, ... (4 entities in total)
• Functional Keywords: center for structural biology of infectious diseases (csbid), histidine kinase, structural genomics, transferase
• Biological source: Vibrio cholerae O1 biovar El Tor str. N16961
• Total number of polymer chains: 8
• Total formula weight: 318913.04

Authors

Minasov, G.,Shuvalova, L.,Brunzelle, J.S.,Wawrzak, Z.,Kiryukhina, O.,Satchell, K.J.F.,Center for Structural Biology of Infectious Diseases (CSBID) (deposition date: 2025-06-19, release date: 2025-08-20, Last modification date: 2026-01-28)

Primary citation

Stanton, V.,Himes, B.,Mejia-Santana, A.,Eppinger, M.,Romo, J.,Xing, J.,Zhulin, I.B.,Cai, H.,Wang, Y.,Inniss, N.l.,Minasov, G.,Satchell, K.J.F.,Klose, K.E.
The PAS domain of the polarly localized histidine kinase FlrB in Vibrio cholerae controls class III flagellar transcription and contributes to intestinal colonization.
Mbio, 16:e0237925-e0237925, 2025

PubMed Abstract: motility is mediated by a single polar flagellum, composed of four flagellin subunits (FlaABCD) in the filament; however, only FlaA is required for motility. Class III flagellar genes, which include , are controlled by the two-component FlrBC system. FlrB is a histidine kinase that phosphorylates FlrC, which activates Class III promoters. The signal(s) that control phosphotransfer between FlrB and FlrC are unknown. A strain lacking the "non-essential" flagellin genes (Δ) is non-motile. Selection for spontaneous motile strains resulted in mutations localized to a Per-Arnt-Sim (PAS) domain in the FlrB N-terminus, including the mutation L36F. The X-ray crystal structure of FlrB revealed an asymmetric dimer with a unique fold of the PAS domain. Transcriptome analysis showed that class III transcription is increased with the addition of the L36F PAS mutation to FlrB, while class III gene transcription was eliminated with a mutation at the site of phosphorylation (H135N). H135N prevents phosphorylation of purified FlrB, whereas L36F increases phosphorylation, indicating these mutations represent "off" and "on" forms of FlrB. FlrB localizes to the cell pole, and localization is dependent on the flagellar polar targeting protein FlhF. strains containing either "off" or "on" forms of FlrB were defective for intestinal colonization in infant mice (10- to 40-fold defect). Our results demonstrate that the PAS domain controls FlrB activity and class III flagellar gene expression, and FlrB must switch between inactive and active forms in order for to successfully colonize the intestine.

PubMed: 40981415
DOI: 10.1128/mbio.02379-25

Experimental method

X-RAY DIFFRACTION (2.75 Å)