TY - JOUR T1 - Molecular Basis of Far-red Sensing in Cyanobacteriochrome JF - bioRxiv DO - 10.1101/2020.06.02.130930 SP - 2020.06.02.130930 AU - Sepalika Bandara AU - Nathan Rockwell AU - Xiaoli Zeng AU - Zhong Ren AU - Cong Wang AU - Heewhan Shin AU - Shelley S. Martin AU - Marcus V. Moreno AU - J. Clark Lagarias AU - Xiaojing Yang Y1 - 2020/01/01 UR - http://biorxiv.org/content/early/2020/06/03/2020.06.02.130930.abstract N2 - Cyanobacteriochromes are small, panchromatic photoreceptors in the phytochrome superfamily that regulate diverse light-mediated adaptive processes in cyanobacteria. The molecular basis of far-red (FR) light perception by cyanobacteriochromes is currently unknown. Here we report the crystal structure of a far-red-sensing cyanobacteriochrome from Anabaena cylindrica PCC 7122, which exhibits a reversible far-red/orange photocycle. The 2.7 Å structure of its FR-absorbing dark state, determined by room temperature serial crystallography and cryo-crystallography, reveals an all-Z,syn configuration of its bound linear tetrapyrrole (bilin) chromophore that is less extended than the bilin chromophores of all known phytochromes. Based on structural comparisons with other bilin-binding proteins and extensive spectral analyses on mutants, we identify key protein-chromophore interactions that enable far-red sensing in bilin-binding proteins. We propose that FR-CBCRs employ two distinct tuning mechanisms, which work together to produce a large batho-chromatic shift. Findings of this work have important implications for development and improvement of photoproteins with far-red absorption and fluorescence.Significance Statement Phytochromes are well known far-red-light sensors found in plants that trigger adaptive responses to facilitate competition for light capture with neighboring plants. Red- and far-red-sensing are critical to cyanobacteria living in the far-red-enriched shade of plants. Here we report the crystal structure of a far-red-sensing cyanobacteriochrome, a distant cyanobacterial relative of phytochrome. These studies shed insight into the poorly understood molecular basis of far-red-sensing by phytobilin-based photoreceptors. Owing to the deep tissue penetration of far-red light, far-red-sensing photoreceptors offer promising protein scaffolds for developing gene-based photoswitches, optoacoustic contrast agents and fluorescent probes for in situ imaging and optogenetic applications.Competing Interest StatementThe authors have declared no competing interest. ER -