Redox driven B12-ligand switch drives CarH photoresponse

Harshwardhan Poddar, Ronald Rios-Santacruz, Derren J. Heyes, Muralidharan Shanmugam, Adam Brookfield, Linus O. Johannissen, Colin W. Levy, Laura N. Jeffreys, Shaowei Zhang, Michiyo Sakuma, Jacques Philippe Colletier, Sam Hay, Giorgio Schirò, Martin Weik, Nigel S. Scrutton, David Leys

Research output: Contribution to journalArticlepeer-review


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 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 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.

Original languageEnglish
Article number5082
JournalNature Communications
Issue number1
Early online date21 Aug 2023
Publication statusPublished - Dec 2023


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