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Title: Structural basis for gene regulation by a B 12-dependent photoreceptor

Abstract

Photoreceptor proteins enable organisms to sense and respond to light. The newly discovered CarH-type photoreceptors use a vitamin B 12 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 B 12 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:
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); USDOE Office of Science (SC), Biological and Environmental Research (BER); National Inst. of Health (NIH) (United States); Ministry of Economy and Competitiveness (Spain); Spanish National Research Council (CSIC) (Spain)
OSTI Identifier:
1225071
Grant/Contract Number:  
AC02-76SF00515; AC02-06CH11357; GM069857; P41GM103393; P41GM103403; BFU2012-40184-C02-01; BFU2012-40184-C02-02
Resource Type:
Journal Article: Accepted Manuscript
Journal Name:
Nature (London)
Additional Journal Information:
Journal Volume: 526; Journal Issue: 7574; Journal ID: ISSN 0028-0836
Publisher:
Nature Publishing Group
Country of Publication:
United States
Language:
ENGLISH
Subject:
59 BASIC BIOLOGICAL SCIENCES; 37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY; X-ray crystallography; Transcription

Citation Formats

Jost, Marco, Fernández-Zapata, Jésus, Polanco, María Carmen, Ortiz-Guerrero, Juan Manuel, Chen, Percival Yang-Ting, Kang, Gyunghoon, Padmanabhan, S., Elías-Arnanz, Montserrat, and Drennan, Catherine L. Structural basis for gene regulation by a B12-dependent photoreceptor. United States: N. p., 2015. Web. doi:10.1038/nature14950.
Jost, Marco, Fernández-Zapata, Jésus, Polanco, María Carmen, Ortiz-Guerrero, Juan Manuel, Chen, Percival Yang-Ting, Kang, Gyunghoon, Padmanabhan, S., Elías-Arnanz, Montserrat, & Drennan, Catherine L. Structural basis for gene regulation by a B12-dependent photoreceptor. United States. https://doi.org/10.1038/nature14950
Jost, Marco, Fernández-Zapata, Jésus, Polanco, María Carmen, Ortiz-Guerrero, Juan Manuel, Chen, Percival Yang-Ting, Kang, Gyunghoon, Padmanabhan, S., Elías-Arnanz, Montserrat, and Drennan, Catherine L. Mon . "Structural basis for gene regulation by a B12-dependent photoreceptor". United States. https://doi.org/10.1038/nature14950. https://www.osti.gov/servlets/purl/1225071.
@article{osti_1225071,
title = {Structural basis for gene regulation by a B12-dependent photoreceptor},
author = {Jost, Marco and Fernández-Zapata, Jésus and Polanco, María Carmen and Ortiz-Guerrero, Juan Manuel and Chen, Percival Yang-Ting and Kang, Gyunghoon and Padmanabhan, S. and Elías-Arnanz, Montserrat and Drennan, Catherine L.},
abstractNote = {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.},
doi = {10.1038/nature14950},
url = {https://www.osti.gov/biblio/1225071}, journal = {Nature (London)},
issn = {0028-0836},
number = 7574,
volume = 526,
place = {United States},
year = {2015},
month = {9}
}

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    Works referencing / citing this record:

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    Total Synthesis, Structure, and Biological Activity of Adenosylrhodibalamin, the Non-Natural Rhodium Homologue of Coenzyme B 12
    journal, June 2016


    Chlorophyll-Derived Yellow Phyllobilins of Higher Plants as Medium-Responsive Chiral Photoswitches
    journal, November 2016


    Optogenetically controlled protein kinases for regulation of cellular signaling
    journal, January 2018


    Green light lithography: a general strategy to create active protein and cell micropatterns
    journal, January 2019


    Modified vitamin B12 derivatives with a peptide backbone for biomimetic studies and medicinal applications
    journal, July 2018


    Green-Light-Induced Inactivation of Receptor Signaling Using Cobalamin-Binding Domains
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    Elucidation of roles for vitamin B 12 in regulation of folate, ubiquinone, and methionine metabolism
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    Prokaryotic Heme Biosynthesis: Multiple Pathways to a Common Essential Product
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