PDBsum entry 4u8h

Circadian clock protein/transcription

PDB id: 4u8h

Contents

Protein chains

490 a.a.

79 a.a.

Metals

_ZN ×2

Waters ×48

PDB id:

4u8h

Name:

Circadian clock protein/transcription

Title:

Crystal structure of mammalian period-cryptochrome complex

Structure:

Cryptochrome-2. Chain: a, c. Fragment: photolyase/cryptochrome alpha/beta domain, residues 1-510. Engineered: yes. Period circadian protein homolog 2. Chain: b, d. Fragment: cry binding domain, residues 1095-1215. Synonym: mper2,circadian clock protein period 2. Engineered: yes

Source:

Mus musculus. Mouse. Organism_taxid: 10090. Gene: cry2, kiaa0658. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Gene: per2.

Resolution:

2.80Å R-factor: 0.209 R-free: 0.278

Authors:

S.N.Nangle,C.Rosensweig,N.Koike,H.Tei,J.S.Takahashi,C.B.Green,N.Zheng

Key ref:

S.N.Nangle et al. (2014). Molecular assembly of the period-cryptochrome circadian transcriptional repressor complex. Elife, 3, e03674. PubMed id: 25127877 DOI: 10.7554/eLife.03674

Date:

03-Aug-14 Release date: 01-Oct-14

Protein chains

Q9R194  (CRY2_MOUSE) -  Cryptochrome-2 from Mus musculus

Seq: 592 a.a.

Struc: 490 a.a.

Protein chains

O54943  (PER2_MOUSE) -  Period circadian protein homolog 2 from Mus musculus

Seq: 1257 a.a.

Struc: 79 a.a.

DOI no: 10.7554/eLife.03674

Elife 3:e03674 (2014)

PubMed id: 25127877

Molecular assembly of the period-cryptochrome circadian transcriptional repressor complex.

S.N.Nangle, C.Rosensweig, N.Koike, H.Tei, J.S.Takahashi, C.B.Green, N.Zheng.

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.