Structural Basis of a Novel Heme Binding Bacterial One-Component Switch

Here, we characterized FG214, a heme binding OCS transcription factor from Fimbriimonas ginsengisoli. The Per-ARNT-Sim (PAS) domain of FG214 binds a hexacoordinate heme b in oxidized conditions and undergoes redox and ligand-dependent conformational changes, transitioning from a monomeric state to an active homodimer.

Spectroscopic and structural data reveal that oxidation stabilizes the Helix-Turn-Helix (HTH)-PAS intramolecular domain interface, while reduction of the heme iron promotes HTH dissociation. Furthermore, addition of imidazole as a ferric heme ligand drives homodimerization and DNA binding. A 1.47 Å crystal structure of an imidazole-bound truncated construct captured an activated dimer, revealing heme coordination sites and homodimerization interfaces.