Interplay between chromophore binding and domain assembly by the B<sub>12</sub>-dependent photoreceptor protein, CarH.
AuthorsCamacho, Inês S; orcid: 0000-0001-9351-8981
Black, Rachelle; orcid: 0000-0002-7067-2385
Heyes, Derren J; orcid: 0000-0002-7453-1571
Johannissen, Linus O; orcid: 0000-0002-0916-9094
Ramakers, Lennart A I
Barran, Perdita E; orcid: 0000-0002-7720-586X
Hay, Sam; orcid: 0000-0003-3274-0938
Jones, Alex R; orcid: 0000-0001-6021-7824
MetadataShow full item record
AbstractOrganisms across the natural world respond to their environment through the action of photoreceptor proteins. The vitamin B<sub>12</sub>-dependent photoreceptor, CarH, is a bacterial transcriptional regulator that controls the biosynthesis of carotenoids to protect against photo-oxidative stress. The binding of B<sub>12</sub> to CarH monomers in the dark results in the formation of a homo-tetramer that complexes with DNA; B<sub>12</sub> 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 B<sub>12</sub>-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 B<sub>12</sub>. When B<sub>12</sub> 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 B<sub>12</sub> is scarcer, as is likely in nature, tetramers with native-like structures can form without a B<sub>12</sub> complement to each monomer, with only one apparently required per head-to-tail dimer. We thus show how a bulky chromophore such as B<sub>12</sub> 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 B<sub>12</sub>-dependent photoreceptors as light-activated tools for biomedical applications.
CitationChemical science, volume 12, issue 24, page 8333-8341
DescriptionFrom Europe PMC via Jisc Publications Router
History: ppub 2021-05-01, epub 2021-05-05
Publication status: Published
Funder: Biotechnology and Biological Sciences Research Council; Grant(s): BB/L002655/1, BB/L016486/1, BB/M011208/1
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