Fig. 1

The photolyase/cryptochrome PHR domain is highly conserved but the intrinsically disordered C-terminal tail is divergent. a E. coli photolyase and the PHR domains of Arabidopsis CRY1, Drosophila CRY, and human CRY1 (solid rectangle) are highly conserved and share an α/β domain containing a secondary pocket (yellow) that can non-covalently bind a secondary antenna chromophore such as MTHF, and an α-helical domain that contains an FAD-binding pocket (green). Not all CRYs bind both chromophores, and while Drosophila CRY binds FAD, human CRY1 does not co-purify with chromophores. Photolyase lacks a C-terminal tail, while cryptochromes from diverse species possess divergent tails (dashed rectangles). b An overlay of the crystal structures of E. coli photolyase (PDB 1DNP, gray) and Drosophila CRY (PDB 4 K03, cyan, tail in magenta) highlighting structural similarities. Both possess an FAD-binding pocket that binds FAD (yellow), and a secondary pocket. The secondary antenna chromophore (MTHF, green) binds to the secondary pocket of photolyase but not Drosophila CRY. The C-terminal tail of Drosophila CRY (magenta) interacts with the FAD pocket. c Cartoon demonstrating how the PHR/tail (cyan/magenta) interaction yields a reversible autoinhibited state. CRY is in an active state when the PHR domain and tail are unbound from each other