Functional motifs in the (6-4) photolyase crystal structure make a comparative framework for DNA repair photolyases and clock cryptochromes

• DOI: 10.1073/pnas.0809180106
• Publication Date: 2009-04-10T01:51:56Z
• Authors: Kenichi Hitomi; Luciano DiTacchio; Andrew S. Arvai; Junpei Yamamoto; Sang-Tae Kim; Takeshi Todo; John A. Tainer; Shigenori Iwai; Satchidananda Panda; Elizabeth D. Getzoff
• Keywords: Photolyase; Flavoprotein

Homologous flavoproteins from the photolyase (PHR)/cryptochrome (CRY) family use FAD cofactor in PHRs to catalyze DNA repair and CRYs tune circadian clock control development. To help address how PHR/CRY members achieve these diverse functions, we determined crystallographic structure of Arabidopsis thaliana (6-4) PHR (UVR3), which is strikingly (>65%) similar sequence human CRYs. The reveals a substrate-binding cavity specific for UV-induced lesion, photoproduct, binding sites different those bacterial consistent with distinct mechanisms activities regulation. Mutational analyses were combined this prototypic PHR/clock CRY cluster identify structural functional motifs: phosphate-binding Pro-Lys-Leu protrusion motifs constricting access above FAD, sulfur loop near external end Trp electron-transfer pathway, previously undefined C-terminal helix. Our results provide detailed, unified framework investigations mammalian Conservation key residues controlling suggests that regulation redox properties radical stability essential not only photoproduct repair, but also clock-regulating functions. reported here elucidate archetypal relationships within flavoprotein suggest local residue tuning, rather than larger modifications, their functions encompassing plant growth development,