3DXC

Crystal structure of the intracellular domain of human APP in complex with Fe65-PTB2


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.10 Å
  • R-Value Free: 0.238 
  • R-Value Work: 0.202 
  • R-Value Observed: 0.204 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Structure of the intracellular domain of the amyloid precursor protein in complex with Fe65-PTB2.

Radzimanowski, J.Simon, B.Sattler, M.Beyreuther, K.Sinning, I.Wild, K.

(2008) EMBO Rep 9: 1134-1140

  • DOI: https://doi.org/10.1038/embor.2008.188
  • Primary Citation of Related Structures:  
    3DXC, 3DXD, 3DXE

  • PubMed Abstract: 

    Cleavage of the amyloid precursor protein (APP) is a crucial event in Alzheimer disease pathogenesis that creates the amyloid-beta peptide (Abeta) and liberates the carboxy-terminal APP intracellular domain (AICD) into the cytosol. The interaction of the APP C terminus with the adaptor protein Fe65 mediates APP trafficking and signalling, and is thought to regulate APP processing and Abeta generation. We determined the crystal structure of the AICD in complex with the C-terminal phosphotyrosine-binding (PTB) domain of Fe65. The unique interface involves the NPxY PTB-binding motif and two alpha helices. The amino-terminal helix of the AICD is capped by threonine T(668), an Alzheimer disease-relevant phosphorylation site involved in Fe65-binding regulation. The structure together with mutational studies, isothermal titration calorimetry and nuclear magnetic resonance experiments sets the stage for understanding T(668) phosphorylation-dependent complex regulation at a molecular level. A molecular switch model is proposed.


  • Organizational Affiliation

    Heidelberg University Biochemistry Center, University of Heidelberg, INF328, D-69120 Heidelberg, Germany.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Amyloid beta A4 protein-binding family B member 1
A, C
140Homo sapiensMutation(s): 0 
Gene Names: APBB1FE65RIR
UniProt & NIH Common Fund Data Resources
Find proteins for O00213 (Homo sapiens)
Explore O00213 
Go to UniProtKB:  O00213
PHAROS:  O00213
GTEx:  ENSG00000166313 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupO00213
Sequence Annotations
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  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Amyloid beta A4 protein
B, D
35Homo sapiensMutation(s): 0 
Gene Names: APPA4AD1
UniProt & NIH Common Fund Data Resources
Find proteins for P05067 (Homo sapiens)
Explore P05067 
Go to UniProtKB:  P05067
PHAROS:  P05067
GTEx:  ENSG00000142192 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP05067
Sequence Annotations
Expand
  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.10 Å
  • R-Value Free: 0.238 
  • R-Value Work: 0.202 
  • R-Value Observed: 0.204 
  • Space Group: P 61
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 114.32α = 90
b = 114.32β = 90
c = 74.85γ = 120
Software Package:
Software NamePurpose
REFMACrefinement
DNAdata collection
MOSFLMdata reduction
SCALAdata scaling
PHASERphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2008-09-16
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2017-02-01
    Changes: Database references
  • Version 1.3: 2024-02-21
    Changes: Data collection, Database references