4I6E

A vertebrate cryptochrome


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.70 Å
  • R-Value Free: 0.287 
  • R-Value Work: 0.244 
  • R-Value Observed: 0.247 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

SCFFBXL3 ubiquitin ligase targets cryptochromes at their cofactor pocket.

Xing, W.Busino, L.Hinds, T.R.Marionni, S.T.Saifee, N.H.Bush, M.F.Pagano, M.Zheng, N.

(2013) Nature 496: 64-68

  • DOI: https://doi.org/10.1038/nature11964
  • Primary Citation of Related Structures:  
    4I6E, 4I6G, 4I6J

  • PubMed Abstract: 

    The cryptochrome (CRY) flavoproteins act as blue-light receptors in plants and insects, but perform light-independent functions at the core of the mammalian circadian clock. To drive clock oscillations, mammalian CRYs associate with the Period proteins (PERs) and together inhibit the transcription of their own genes. The SCF(FBXL3) ubiquitin ligase complex controls this negative feedback loop by promoting CRY ubiquitination and degradation. However, the molecular mechanisms of their interactions and the functional role of flavin adenine dinucleotide (FAD) binding in CRYs remain poorly understood. Here we report crystal structures of mammalian CRY2 in its apo, FAD-bound and FBXL3-SKP1-complexed forms. Distinct from other cryptochromes of known structures, mammalian CRY2 binds FAD dynamically with an open cofactor pocket. Notably, the F-box protein FBXL3 captures CRY2 by simultaneously occupying its FAD-binding pocket with a conserved carboxy-terminal tail and burying its PER-binding interface. This novel F-box-protein-substrate bipartite interaction is susceptible to disruption by both FAD and PERs, suggesting a new avenue for pharmacological targeting of the complex and a multifaceted regulatory mechanism of CRY ubiquitination.


  • Organizational Affiliation

    Department of Pharmacology, University of Washington, Seattle, Washington 98195, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Cryptochrome-2512Mus 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
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.70 Å
  • R-Value Free: 0.287 
  • R-Value Work: 0.244 
  • R-Value Observed: 0.247 
  • Space Group: P 43
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 68.935α = 90
b = 68.935β = 90
c = 127.528γ = 90
Software Package:
Software NamePurpose
HKL-2000data collection
PHENIXmodel building
PHENIXrefinement
HKL-2000data reduction
HKL-2000data scaling
PHENIXphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2013-03-13
    Type: Initial release
  • Version 1.1: 2013-05-01
    Changes: Database references
  • Version 1.2: 2023-09-20
    Changes: Data collection, Database references, Refinement description