1YA9

Crystal Structure of the 22kDa N-Terminal Fragment of Mouse Apolipoprotein E


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.09 Å
  • R-Value Free: 0.224 
  • R-Value Work: 0.215 
  • R-Value Observed: 0.215 

wwPDB Validation   3D Report Full Report


This is version 1.4 of the entry. See complete history


Literature

Engineering conformational destabilization into mouse apolipoprotein E. A model for a unique property of human apolipoprotein E4

Hatters, D.M.Peters-Libeu, C.A.Weisgraber, K.H.

(2005) J Biol Chem 280: 26477-26482

  • DOI: https://doi.org/10.1074/jbc.M503910200
  • Primary Citation of Related Structures:  
    1YA9

  • PubMed Abstract: 

    Apolipoprotein (apo) E4 is a major risk factor for Alzheimer and cardiovascular diseases. ApoE4 differs from the two other common isoforms (apoE2 and apoE3) by its lower resistance to denaturation and greater propensity to form partially folded intermediates. As a first step to determine the importance of stability differences in vivo, we reengineered a partially humanized variant of the amino-terminal domain of mouse apoE (T61R mouse apoE) to acquire a destabilized conformation like that of apoE4. For this process, we determined the crystal structure of wild-type mouse apoE, which, like apoE4, forms a four-helix bundle, and identified two structural differences in the turn between helices 2 and 3 and in the middle of helix 3 as potentially destabilizing sites. Introducing mutations G83T and N113G at these sites destabilized the mouse apoE conformation. The mutant mouse apoE more rapidly remodeled phospholipid than T61R mouse apoE, which supports the hypothesis that a destabilized conformation promotes apoE4 lipid binding.


  • Organizational Affiliation

    Gladstone Institute of Neurological Disease, San Francisco, California 94158, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Apolipoprotein E181Mus musculusMutation(s): 0 
Gene Names: Apoe
Membrane Entity: Yes 
UniProt & NIH Common Fund Data Resources
Find proteins for P08226 (Mus musculus)
Explore P08226 
Go to UniProtKB:  P08226
IMPC:  MGI:88057
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP08226
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.09 Å
  • R-Value Free: 0.224 
  • R-Value Work: 0.215 
  • R-Value Observed: 0.215 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 29.034α = 90
b = 49.233β = 90
c = 112.177γ = 90
Software Package:
Software NamePurpose
CNSrefinement
DENZOdata reduction
CCP4data scaling
EPMRphasing
REFMACrefinement

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2005-06-07
    Type: Initial release
  • Version 1.1: 2008-04-30
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2019-07-24
    Changes: Data collection, Refinement description
  • Version 1.4: 2024-02-14
    Changes: Data collection, Database references