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Title: Structural basis for gene regulation by a B12-dependent photoreceptor

Photoreceptor proteins enable organisms to sense and respond to light. The newly discovered CarH-type photoreceptors use a vitamin B12 derivative, adenosylcobalamin, as the light-sensing chromophore to mediate light-dependent gene regulation. Here in this paper, we present crystal structures of Thermus thermophilus CarH in all three relevant states: in the dark, both free and bound to operator DNA, and after light exposure. These structures provide visualizations of how adenosylcobalamin mediates CarH tetramer formation in the dark, how this tetramer binds to the promoter -35 element to repress transcription, and how light exposure leads to a large-scale conformational change that activates transcription. In addition to the remarkable functional repurposing of adenosylcobalamin from an enzyme cofactor to a light sensor, we find that nature also repurposed two independent protein modules in assembling CarH. Finally, these results expand the biological role of vitamin B12 and provide fundamental insight into a new mode of light-dependent gene regulation.
Authors:
 [1] ;  [2] ;  [3] ;  [3] ;  [1] ;  [1] ;  [2] ;  [3] ;  [4]
  1. Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States). Dept. of Chemistry
  2. Spanish National Research Council (CSIC), Madrid (Spain). Inst. of Physical Chemistry "Rocasolano"
  3. Univ. of Murcia (Spain). Faculty of Biology. Dept. of Genetics and Microbiology. Area of Genetics
  4. Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States). Dept. of Chemistry. Dept. of Biology. Howard Hughes Medical Inst.
Publication Date:
OSTI Identifier:
1225071
Grant/Contract Number:
AC02-76SF00515; AC02-06CH11357; GM069857; P41GM103393; P41GM103403; BFU2012-40184-C02-01; BFU2012-40184-C02-02
Type:
Accepted Manuscript
Journal Name:
Nature (London)
Additional Journal Information:
Journal Name: Nature (London); Journal Volume: 526; Journal Issue: 7574; Journal ID: ISSN 0028-0836
Publisher:
Nature Publishing Group
Research Org:
Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States); Spanish National Research Council (CSIC), Madrid (Spain); Univ. of Murcia (Spain)
Sponsoring Org:
USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22); USDOE Office of Science (SC), Biological and Environmental Research (BER) (SC-23); National Inst. of Health (NIH) (United States); Ministry of Economy and Competitiveness (Spain); Spanish National Research Council (CSIC) (Spain)
Country of Publication:
United States
Language:
ENGLISH
Subject:
59 BASIC BIOLOGICAL SCIENCES; 37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY; X-ray crystallography; Transcription