Journal Article

Structural basis for gene regulation by a B12-dependent photoreceptor

Elías-Arnanz, Montserrat, Jost, Marco, Fernández-Zapata, Jésus, Polanco, María Carmen, Ortiz-Guerrero, Juan Manuel, Kang, Gyunghoon, Padmanabhan, S., Chen, Percival Yang-Ting, Drennan, Catherine L.

2015

Overview

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 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. These results expand the biological role of vitamin B 12 and provide fundamental insight into a new mode of light-dependent gene regulation. Crystal structures are presented of Thermus thermophilus CarH, a photoreceptor that uses a vitamin B 12 derivative, in all three relevant states: in the dark, both free and bound to operator DNA, and after light exposure. New insights into light-dependent gene regulation CarH is a photoreceptor that mediates light-dependent gene regulation in Myxococcus xanthus and Thermus thermophilus , using the vitamin B 12 derivative, adenosylcobalamin, as the light-sensing chromophore. Catherine Drennan and colleagues have solved X-ray crystal structures of CarH in all three relevant states: in the dark, both free and bound to operator DNA, and after light exposure. The structures reveal how exposure to light triggers large conformational changes that lead to the disassociation of CarH from DNA and relief of CarH-mediated transcriptional repression of carotenoid biosynthetic genes.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 42/70 / 631/337/572 / 631/535/1266 / 82/16 / 82/29 / 82/80 / 82/83 / Amino Acid Sequence / Bacterial Proteins - chemistry / Bacterial Proteins - genetics / Bacterial Proteins - metabolism / Base Sequence / BASIC BIOLOGICAL SCIENCES / Cobamides - metabolism / Cobamides - radiation effects / Crystallography, X-Ray / Darkness / Dimerization / DNA, Bacterial - genetics / DNA, Bacterial - metabolism / Gene Expression Regulation, Bacterial - radiation effects / Humanities and Social Sciences / INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY / Light / Models, Molecular / Molecular Sequence Data / multidisciplinary / Operator Regions, Genetic - genetics / Promoter Regions, Genetic - genetics / Protein Structure, Quaternary - radiation effects / Science / Thermus thermophilus - chemistry / Thermus thermophilus - genetics / Thermus thermophilus - radiation effects / Transcription / Transcription, Genetic - genetics / Transcription, Genetic - radiation effects / Vitamin B 12 - metabolism / Vitamin B 12 - radiation effects / X-ray crystallography