Back

PAS domain of flagellar histidine kinase FlrB exhibits novel architecture, and binds Heme as sensory signal in unconventional fashion

Mukherjee, P.; Agarwal, S.; Basu Mallick, S.; Dasgupta, J.

2023-06-29 biophysics
10.1101/2023.06.29.547052 bioRxiv
Show abstract

Phosphorylation of the {sigma}54-dependent transcription activator FlrC by the sensor histidine kinase FlrB is essential in flagellar synthesis of Vibrio cholerae. Despite that, the structure, sensory signal, and mechanistic basis of function of FlrB were elusive. Here we report the crystal structure of the sensory PAS domain of FlrB in functional dimeric state that exhibits a novel architecture. Series of biochemical/biophysical experiments unequivocally established heme as sensory ligand that packs hydrophobically in the ligand binding cleft of FlrB-PAS. Intriguingly, ATP binding to the C-terminal ATP binding (CA) domain assists PAS domain to bind heme, vis-a-vis, heme binding to the PAS facilitates ATP binding to CA; suggesting a synergistic mode of heme and ATP binding to FlrB. We propose that such synergistic binding triggers conformational signaling in FlrB, leading to the downstream flagellar gene transcription. Enhanced swimming motility of V. cholerae with increased heme uptake further supports this proposition.

Matching journals

The top 8 journals account for 50% of the predicted probability mass.

50% of probability mass above

"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.