Macromolecular Assemblies of the Mammalian Circadian Clock

An ∼1.9-MDa repressor assembly was identified in mouse liver nuclei that includes all three PER proteins, both CRY proteins, and Casein Kinase-1δ (CK1δ).

• The repressor assembly quantitatively incorporates the CLOCK-BMAL1 transcription factor target.
• CLOCK-BMAL1 exists in an ∼750-kDa complex prior to its incorporation into the repressor assembly.
• Single-particle electron microscopy revealed that nuclear PER complexes are quasi-spherical structures measuring ∼40 nm.
• In the cytoplasm, PERs, CRYs, and CK1δ form several complexes of ∼0.9-1.1 MDa, suggesting a regulated assembly pathway.
• GAPVD1, a cytoplasmic trafficking factor, may regulate the assembly of these complexes.
• Two purified cytoplasmic PER complexes were characterized as ∼20-nm and ∼25-nm structures with flexibly tethered globular domains.

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