| First Author | Aryal RP | Year | 2017 |
| Journal | Mol Cell | Volume | 67 |
| Issue | 5 | Pages | 770-782.e6 |
| PubMed ID | 28886335 | Mgi Jnum | J:256785 |
| Mgi Id | MGI:6106719 | Doi | 10.1016/j.molcel.2017.07.017 |
| Citation | Aryal RP, et al. (2017) Macromolecular Assemblies of the Mammalian Circadian Clock. Mol Cell 67(5):770-782.e6 |
| abstractText | The mammalian circadian clock is built on a feedback loop in which PER and CRY proteins repress their own transcription. We found that in mouse liver nuclei all three PERs, both CRYs, and Casein Kinase-1delta (CK1delta) are present together in an approximately 1.9-MDa repressor assembly that quantitatively incorporates its CLOCK-BMAL1 transcription factor target. Prior to incorporation, CLOCK-BMAL1 exists in an approximately 750-kDa complex. Single-particle electron microscopy (EM) revealed nuclear PER complexes purified from mouse liver to be quasi-spherical approximately 40-nm structures. In the cytoplasm, PERs, CRYs, and CK1delta were distributed into several complexes of approximately 0.9-1.1 MDa that appear to constitute an assembly pathway regulated by GAPVD1, a cytoplasmic trafficking factor. Single-particle EM of two purified cytoplasmic PER complexes revealed approximately 20-nm and approximately 25-nm structures, respectively, characterized by flexibly tethered globular domains. Our results define the macromolecular assemblies comprising the circadian feedback loop and provide an initial structural view of endogenous eukaryotic clock machinery. |
