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Issue 24, 2021
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Interplay between chromophore binding and domain assembly by the B12-dependent photoreceptor protein, CarH

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Abstract

Organisms across the natural world respond to their environment through the action of photoreceptor proteins. The vitamin B12-dependent photoreceptor, CarH, is a bacterial transcriptional regulator that controls the biosynthesis of carotenoids to protect against photo-oxidative stress. The binding of B12 to CarH monomers in the dark results in the formation of a homo-tetramer that complexes with DNA; B12 photochemistry results in tetramer dissociation, releasing DNA for transcription. Although the details of the response of CarH to light are beginning to emerge, the biophysical mechanism of B12-binding in the dark and how this drives domain assembly is poorly understood. Here – using a combination of molecular dynamics simulations, native ion mobility mass spectrometry and time-resolved spectroscopy – we reveal a complex picture that varies depending on the availability of B12. When B12 is in excess, its binding drives structural changes in CarH monomers that result in the formation of head-to-tail dimers. The structural changes that accompany these steps mean that they are rate-limiting. The dimers then rapidly combine to form tetramers. Strikingly, when B12 is scarcer, as is likely in nature, tetramers with native-like structures can form without a B12 complement to each monomer, with only one apparently required per head-to-tail dimer. We thus show how a bulky chromophore such as B12 shapes protein/protein interactions and in turn function, and how a protein can adapt to a sub-optimal availability of resources. This nuanced picture should help guide the engineering of B12-dependent photoreceptors as light-activated tools for biomedical applications.

Graphical abstract: Interplay between chromophore binding and domain assembly by the B12-dependent photoreceptor protein, CarH

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Article information


Submitted
27 Jan 2021
Accepted
04 May 2021
First published
05 May 2021

This article is Open Access
All publication charges for this article have been paid for by the Royal Society of Chemistry

Chem. Sci., 2021,12, 8333-8341
Article type
Edge Article

Interplay between chromophore binding and domain assembly by the B12-dependent photoreceptor protein, CarH

I. S. Camacho, R. Black, D. J. Heyes, L. O. Johannissen, L. A. I. Ramakers, B. Bellina, P. E. Barran, S. Hay and A. R. Jones, Chem. Sci., 2021, 12, 8333
DOI: 10.1039/D1SC00522G

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    [Original citation] - Published by The Royal Society of Chemistry (RSC) on behalf of the Centre National de la Recherche Scientifique (CNRS) and the RSC.
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    [Original citation] - Published by the PCCP Owner Societies.
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    [Original citation] - Published by The Royal Society of Chemistry (RSC) on behalf of the European Society for Photobiology, the European Photochemistry Association, and RSC.
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    [Original citation] - Published by The Royal Society of Chemistry.

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