Interplay between chromophore binding and domain assembly by the B
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
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AbstractOrganisms across the natural world respond to their environment through the action of photoreceptor proteins. The vitamin B -dependent photoreceptor, CarH, is a bacterial transcriptional regulator that controls the biosynthesis of carotenoids to protect against photo-oxidative stress. The binding of B to CarH monomers in the dark results in the formation of a homo-tetramer that complexes with DNA; B 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 -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 . When B 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 is scarcer, as is likely in nature, tetramers with native-like structures can form without a B complement to each monomer, with only one apparently required per head-to-tail dimer. We thus show how a bulky chromophore such as B 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 -dependent photoreceptors as light-activated tools for biomedical applications. [Abstract copyright: This journal is © The Royal Society of Chemistry.]
CitationChemical science, volume 12, issue 24, page 8333-8341
DescriptionFrom PubMed via Jisc Publications Router
Publication status: epublish
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