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Biological Chemistry

Vitamin B-12 Expands Its Regulatory Role

Bioinorganic Chemistry: Structural study unveils how adenosylcobalamin helps guide light-dependent gene regulation

by Stephen K. Ritter
October 5, 2015 | APPEARED IN VOLUME 93, ISSUE 39

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Credit: MIT
When adenosylcobalamin in the bacteria, used here to spell out “B12,” senses light, it fluoresces.
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Credit: MIT
When adenosylcobalamin in the bacteria, used here to spell out “B12,” senses light, it fluoresces.

Adenosylcobalamin, one of the active forms of vitamin B-12, is known for its job as a cofactor in radical-based enzyme reactions and as a modulator of gene expression via mRNA riboswitches. Scientists have more recently discovered that many bacteria also use the molecule as a light-capturing chromophore for photoreceptor proteins that help protect cells from sunlight-induced DNA damage. Researchers are now reporting the mechanistic details behind this new process (Nature 2015, DOI: 10.1038/nature14950). Marco Jost and Catherine L. Drennan of MIT, along with S. Padmanabhan of the Institute of Physical Chemistry Rocasolano, in Madrid, and Montserrat Elías-Arnanz of the University of Murcia, in Spain, and coworkers obtained X-ray crystal structures of one photoreceptor protein, the transcription factor CarH, in three different states—in the dark, bound to DNA, and after being exposed to light. The structural snapshots reveal how, in the dark, adenosylcobalamin guides formation of a CarH tetramer that binds DNA to prevent transcription. When light hits the bacteria, it photolyzes adenosylcobalamin and induces a conformational change in CarH that causes the protein complex to dissociate from DNA, which triggers the bacteria to express genes that produce carotenoid molecules to counter light-induced oxidative damage. These mechanistic details could help scientists develop light-directed control of gene transcription or methods to control interactions between proteins.

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