Fig. 3

The human CRY1 tail regulates multiple sites on the PHR domain. a The hCRY1 tail is composed of exons 10 (residues 496–529), exon 11 (residues 530–553), and exon 12 (residues 554–586). NMR chemical shift mapping identified distinct linear motifs in exons 10 and 11 (pink) that may be involved in binding directly to the PHR domain [35]. DNA-PK-dependent phosphorylation sites in exons 11 and 12 are marked below a circled ‘P’ [36]. b The PER2 CBD (orange) wraps around the CRY1 PHR domain (purple) near regions where the hCRY1 tail might also interact, such as the CC-helix, FAD-binding pocket (KL101 is a CRY1-selective ligand, cyan) and the secondary pocket (green) in PDBs 6KX6, KL101-bound and 6OF7, PER2 CBD-bound. Thin dashed lines indicate flexible regions on the PHR domain that were missing density. c A possible model for how the tail (magenta) might bind to both the FAD-binding pocket and the secondary pocket on the PHR domain in the absence of PER proteins. Exon 10 has been implicated at binding near the FAD-binding pocket [37], while exon 11 inhibits CLOCK PAS-B binding at the secondary pocket and deletion of exon 12 has no effect on affinity of the tail for the PHR domain [35]