Formation of a repressive complex in the mammalian circadian clock is mediated by the secondary pocket of CRY1

CRY1 directly binds to the PAS domain core of CLOCK:BMAL1, influencing circadian gene expression.

• The CLOCK:BMAL1 complex is central to the mammalian circadian rhythm, regulating approximately 24-hour gene expression cycles.
• A repressive complex involving CRY1, CLOCK, and BMAL1 is crucial for the transition from gene repression to activation.
• CRY1's binding to the CLOCK PAS-B domain is primarily driven by its interaction with a specific part of this domain.
• Modeling and X-ray scattering reveal that a key loop of the CLOCK PAS-B domain fits into a particular pocket of CRY1.
• Mutations at the binding interface of either CRY1 or CLOCK can disrupt the formation of the ternary complex, affecting CLOCK:BMAL1 regulation.

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