Arg-293 in Cryptochrome1 helps control how it binds to CLOCK protein in the body’s daily rhythm

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

• CRY1 and CRY2 are components of circadian clocks, with CRY1 having a higher binding affinity to the BMAL1/CLOCK complex than CRY2.
• The serine-rich loop of CRYs is regulated by Arg-293 of CRY1, which is affected by a specific genetic variant.
• The p.Arg293His variant leads to reduced repressor activity on BMAL1/CLOCK-driven transcription.
• In the absence of PER2, the variant exhibits a lower affinity for the BMAL1/CLOCK complex compared to normal CRY1.
• Molecular dynamics simulations indicate that the p.Arg293His variant decreases the dynamicity of the serine-rich loop, influencing communication pathways.

Simplified