The Arg-293 of Cryptochrome1 is responsible for the allosteric regulation of CLOCK-CRY1 binding in circadian rhythm

The p.Arg293His variant of CRY1 is associated with a shortened circadian period in a double knockout mouse embryonic fibroblast cell line.

• CRY1 binds more strongly to the BMAL1/CLOCK complex than CRY2, affecting circadian rhythm regulation.
• The p.Arg293His variant reduces CRY1's repressor activity on BMAL1/CLOCK driven transcription.
• This variant's impact on circadian rhythm may be due to decreased affinity for BMAL1/CLOCK in the absence of PER2.
• Molecular dynamics simulations indicate that the p.Arg293His variant decreases the flexibility of a key loop in CRY1.
• Allosteric regulation of CRY1 is vital for the proper functioning of circadian clocks.

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