PDBsum entry 4u8h

Circadian clock protein/transcription

PDB id: 4u8h

Contents

Protein chains

490 a.a.

79 a.a.

Metals

_ZN ×2

Waters ×48

References listed in PDB file

Key reference

• Title: Molecular assembly of the period-Cryptochrome circadian transcriptional repressor complex.
• Authors: S.N.Nangle, C.Rosensweig, N.Koike, H.Tei, J.S.Takahashi, C.B.Green, N.Zheng.
• Ref.: Elife, 2014, 3, e03674. [DOI no: 10.7554/eLife.03674]
• PubMed id: 25127877

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.DOI: http://dx.doi.org/10.7554/eLife.03674.001.