4U8H

Crystal Structure of Mammalian Period-Cryptochrome Complex


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.80 Å
  • R-Value Free: 0.278 
  • R-Value Work: 0.205 
  • R-Value Observed: 0.209 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

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

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

(2014) Elife 3: e03674-e03674

  • DOI: https://doi.org/10.7554/eLife.03674
  • Primary Citation of Related Structures:  
    4U8H

  • 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.


  • Organizational Affiliation

    Department of Pharmacology, University of Washington, Seattle, United States.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Cryptochrome-2A,
B [auth C]
510Mus musculusMutation(s): 0 
Gene Names: Cry2Kiaa0658
UniProt
Find proteins for Q9R194 (Mus musculus)
Explore Q9R194 
Go to UniProtKB:  Q9R194
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ9R194
Sequence Annotations
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  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Period circadian protein homolog 2C [auth B],
D
121Mus musculusMutation(s): 0 
Gene Names: Per2
UniProt & NIH Common Fund Data Resources
Find proteins for O54943 (Mus musculus)
Explore O54943 
Go to UniProtKB:  O54943
IMPC:  MGI:1195265
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupO54943
Sequence Annotations
Expand
  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.80 Å
  • R-Value Free: 0.278 
  • R-Value Work: 0.205 
  • R-Value Observed: 0.209 
  • Space Group: P 41
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 97.675α = 90
b = 97.675β = 90
c = 163.213γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement

Structure Validation

View Full Validation Report



Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
National Institutes of Health/National Cancer Institute (NIH/NCI)United StatesR01-CA107134
Howard Hughes Medical Institute (HHMI)United States--
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)United StatesT32-GM007750

Revision History  (Full details and data files)

  • Version 1.0: 2014-10-01
    Type: Initial release
  • Version 1.1: 2017-09-20
    Changes: Author supporting evidence, Derived calculations, Other, Source and taxonomy
  • Version 1.2: 2019-11-20
    Changes: Author supporting evidence
  • Version 1.3: 2023-09-27
    Changes: Data collection, Database references, Derived calculations, Refinement description