6OF7
Crystal structure of the CRY1-PER2 complex
Summary for 6OF7
| Entry DOI | 10.2210/pdb6of7/pdb |
| Descriptor | Cryptochrome-1, Period circadian protein homolog 2 (2 entities in total) |
| Functional Keywords | cryptochrome-1, period 2 complex, circadian clock protein |
| Biological source | Mus musculus (Mouse) More |
| Total number of polymer chains | 2 |
| Total formula weight | 71196.33 |
| Authors | Michael, A.K.,Fribourgh, J.L.,Tripathi, S.M.,Partch, C.L. (deposition date: 2019-03-28, release date: 2020-03-04, Last modification date: 2023-10-11) |
| Primary citation | Fribourgh, J.L.,Srivastava, A.,Sandate, C.R.,Michael, A.K.,Hsu, P.L.,Rakers, C.,Nguyen, L.T.,Torgrimson, M.R.,Parico, G.C.G.,Tripathi, S.,Zheng, N.,Lander, G.C.,Hirota, T.,Tama, F.,Partch, C.L. Dynamics at the serine loop underlie differential affinity of cryptochromes for CLOCK:BMAL1 to control circadian timing. Elife, 9:-, 2020 Cited by PubMed Abstract: Mammalian circadian rhythms are generated by a transcription-based feedback loop in which CLOCK:BMAL1 drives transcription of its repressors (PER1/2, CRY1/2), which ultimately interact with CLOCK:BMAL1 to close the feedback loop with ~24 hr periodicity. Here we pinpoint a key difference between CRY1 and CRY2 that underlies their differential strengths as transcriptional repressors. Both cryptochromes bind the BMAL1 transactivation domain similarly to sequester it from coactivators and repress CLOCK:BMAL1 activity. However, we find that CRY1 is recruited with much higher affinity to the PAS domain core of CLOCK:BMAL1, allowing it to serve as a stronger repressor that lengthens circadian period. We discovered a dynamic serine-rich loop adjacent to the secondary pocket in the photolyase homology region (PHR) domain that regulates differential binding of cryptochromes to the PAS domain core of CLOCK:BMAL1. Notably, binding of the co-repressor PER2 remodels the serine loop of CRY2, making it more CRY1-like and enhancing its affinity for CLOCK:BMAL1. PubMed: 32101164DOI: 10.7554/eLife.55275 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (3.11 Å) |
Structure validation
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