3QD2

Crystal structure of mouse PERK kinase domain


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.81 Å
  • R-Value Free: 0.332 
  • R-Value Work: 0.270 
  • R-Value Observed: 0.273 

wwPDB Validation   3D Report Full Report


This is version 1.4 of the entry. See complete history


Literature

The structure of the PERK kinase domain suggests the mechanism for its activation.

Cui, W.Li, J.Ron, D.Sha, B.

(2011) Acta Crystallogr D Biol Crystallogr 67: 423-428

  • DOI: https://doi.org/10.1107/S0907444911006445
  • Primary Citation of Related Structures:  
    3QD2

  • PubMed Abstract: 

    The endoplasmic reticulum (ER) unfolded protein response (UPR) is comprised of several intracellular signaling pathways that alleviate ER stress. The ER-localized transmembrane kinase PERK is one of three major ER stress transducers. Oligomerization of PERK's N-terminal ER luminal domain by ER stress promotes PERK trans-autophosphorylation of the C-terminal cytoplasmic kinase domain at multiple residues including Thr980 on the kinase activation loop. Activated PERK phosphorylates Ser51 of the α-subunit of translation initiation factor 2 (eIF2α), which inhibits initiation of protein synthesis and reduces the load of unfolded proteins entering the ER. The crystal structure of PERK's kinase domain has been determined to 2.8 Å resolution. The structure resembles the back-to-back dimer observed in the related eIF2α kinase PKR. Phosphorylation of Thr980 stabilizes both the activation loop and helix αG in the C-terminal lobe, preparing the latter for eIF2α binding. The structure suggests conservation in the mode of activation of eIF2α kinases and is consistent with a `line-up' model for PERK activation triggered by oligomerization of its luminal domain.


  • Organizational Affiliation

    Department of Cell Biology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Eukaryotic translation initiation factor 2-alpha kinase 3A [auth B]332Mus musculusMutation(s): 0 
Gene Names: Eif2ak3
EC: 2.7.11.1
UniProt
Find proteins for Q9Z2B5 (Mus musculus)
Explore Q9Z2B5 
Go to UniProtKB:  Q9Z2B5
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ9Z2B5
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
TPO
Query on TPO
A [auth B]L-PEPTIDE LINKINGC4 H10 N O6 PTHR
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.81 Å
  • R-Value Free: 0.332 
  • R-Value Work: 0.270 
  • R-Value Observed: 0.273 
  • Space Group: P 41 21 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 97.891α = 90
b = 97.891β = 90
c = 116.706γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
PDB_EXTRACTdata extraction
HKL-2000data collection
HKL-2000data reduction
SCALEPACKdata scaling
PHASESphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2011-04-27
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2012-03-21
    Changes: Database references
  • Version 1.3: 2017-07-26
    Changes: Refinement description, Source and taxonomy
  • Version 1.4: 2019-01-16
    Changes: Data collection, Structure summary