Abstract CarH is a coenzyme B12-dependent photoreceptor involved in regulating carotenoid biosynthesis.How light-triggered cleavage of the B12 Co-C bond culminates in CarH tetramer dissociation to initiate transcription remains unclear.Here, a series of crystal structures of the CarH B12-binding domain after illumination suggest formation of unforeseen intermediate states prior to tetramer dissociation.Unexpectedly, in the absence of oxygen, Co-C bond cleavage is followed by reorientation Baby of the corrin ring and a switch from a lower to upper histidine-Co ligation, corresponding to a pentacoordinate state.
Under aerobic conditions, rapid flash-cooling of crystals prior to deterioration upon illumination confirm a similar B12-ligand switch occurs.Removal of the upper His-ligating residue prevents monomer formation upon illumination.Combined with DEEP CONDITIONING MINERAL HAIR MASK detailed solution spectroscopy and computational studies, these data demonstrate the CarH photoresponse integrates B12 photo- and redox-chemistry to drive large-scale conformational changes through stepwise Co-ligation changes.