4U8H

Crystal Structure of Mammalian Period-Cryptochrome Complex

Summary for 4U8H

• Entry DOI: 10.2210/pdb4u8h/pdb
• Descriptor: Cryptochrome-2, Period circadian protein homolog 2, ZINC ION, ... (4 entities in total)
• Functional Keywords: transcriptional repression, zinc-binding, circadian clock protein-transcription complex, circadian clock protein/transcription
• Biological source: Mus musculus (Mouse); More
• Total number of polymer chains: 4
• Total formula weight: 144739.35

Authors

Nangle, S.N.,Rosensweig, C.,Koike, N.,Tei, H.,Takahashi, J.S.,Green, C.B.,Zheng, N. (deposition date: 2014-08-03, release date: 2014-10-01, Last modification date: 2024-10-23)

Primary citation

Nangle, S.N.,Rosensweig, C.,Koike, N.,Tei, H.,Takahashi, J.S.,Green, C.B.,Zheng, N.
Molecular assembly of the period-cryptochrome circadian transcriptional repressor complex.
Elife, 3:e03674-e03674, 2014

PubMed Abstract: The mammalian circadian clock is driven by a transcriptional-translational feedback loop, which produces robust 24-hr rhythms. Proper oscillation of the clock depends on the complex formation and periodic turnover of the Period and Cryptochrome proteins, which together inhibit their own transcriptional activator complex, CLOCK-BMAL1. We determined the crystal structure of the CRY-binding domain (CBD) of PER2 in complex with CRY2 at 2.8 Å resolution. PER2-CBD adopts a highly extended conformation, embracing CRY2 with a sinuous binding mode. Its N-terminal end tucks into CRY adjacent to a large pocket critical for CLOCK-BMAL1 binding, while its C-terminal half flanks the CRY2 C-terminal helix and sterically hinders the recognition of CRY2 by the FBXL3 ubiquitin ligase. Unexpectedly, a strictly conserved intermolecular zinc finger, whose integrity is important for clock rhythmicity, further stabilizes the complex. Our structure-guided analyses show that these interspersed CRY-interacting regions represent multiple functional modules of PERs at the CRY-binding interface.

PubMed: 25127877
DOI: 10.7554/eLife.03674

Experimental method

X-RAY DIFFRACTION (2.798 Å)