6OF7

Crystal structure of the CRY1-PER2 complex

6OF7 の概要

• エントリーDOI: 10.2210/pdb6of7/pdb
• 分子名称: Cryptochrome-1, Period circadian protein homolog 2 (2 entities in total)
• 機能のキーワード: cryptochrome-1, period 2 complex, circadian clock protein
• 由来する生物種: Mus musculus (Mouse); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 71196.33

構造登録者

Michael, A.K.,Fribourgh, J.L.,Tripathi, S.M.,Partch, C.L. (登録日: 2019-03-28, 公開日: 2020-03-04, 最終更新日: 2023-10-11)

主引用文献

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

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: 32101164
DOI: 10.7554/eLife.55275

実験手法

X-RAY DIFFRACTION (3.11 Å)