3Q7L

Crystal structure of the E2 domain of amyloid precursor-like protein 1


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.20 Å
  • R-Value Free: 0.256 
  • R-Value Work: 0.216 
  • R-Value Observed: 0.220 

wwPDB Validation   3D Report Full Report


This is version 1.4 of the entry. See complete history


Literature

Crystal Structure of the E2 Domain of Amyloid Precursor Protein-like Protein 1 in Complex with Sucrose Octasulfate.

Xue, Y.Lee, S.Wang, Y.Ha, Y.

(2011) J Biol Chem 286: 29748-29757

  • DOI: https://doi.org/10.1074/jbc.M111.219659
  • Primary Citation of Related Structures:  
    3Q7G, 3Q7L

  • PubMed Abstract: 

    Missense mutations in the amyloid precursor protein (APP) gene can cause familial Alzheimer disease. It is thought that APP and APP-like proteins (APLPs) may play a role in adhesion and signal transduction because their ectodomains interact with components of the extracellular matrix. Heparin binding induces dimerization of APP and APLPs. To help explain how these proteins interact with heparin, we have determined the crystal structure of the E2 domain of APLP1 in complex with sucrose octasulfate (SOS). A total of three SOS molecules are bound to the E2 dimer. Two SOSs are bound inside a narrow intersubdomain groove, and the third SOS is bound near the two-fold axis of the protein. Mutational analyses show that most residues interacting with SOS also contribute to heparin binding, although in varying degrees; a deep pocket, defined by His-376, Lys-422, and Arg-429, and an interfacial site between Lys-314 and its symmetry mate are most important in the binding of the negatively charged polysaccharide. Comparison with a lower resolution APP structure shows that all key heparin binding residues are conserved and identically positioned, suggesting that APLP1 and APP may bind heparin similarly. In transfected HEK-293 cells, mutating residues responsible for heparin binding causes little change in the proteolysis of APP by the secretases. However, mutating a pair of conserved basic residues (equivalent to Arg-414 and Arg-415 of APLP1) immediately adjacent to the heparin binding site affects both the maturation and the processing of APP.


  • Organizational Affiliation

    Department of Pharmacology, Yale School of Medicine, New Haven, Connecticut 06520, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Amyloid-like protein 1
A, B
214Homo sapiensMutation(s): 0 
Gene Names: APLP1
UniProt & NIH Common Fund Data Resources
Find proteins for P51693 (Homo sapiens)
Explore P51693 
Go to UniProtKB:  P51693
PHAROS:  P51693
GTEx:  ENSG00000105290 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP51693
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.20 Å
  • R-Value Free: 0.256 
  • R-Value Work: 0.216 
  • R-Value Observed: 0.220 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 72.953α = 90
b = 83.045β = 90
c = 89.242γ = 90
Software Package:
Software NamePurpose
CBASSdata collection
PHASERphasing
REFMACrefinement
DENZOdata reduction
SCALEPACKdata scaling

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

  • Released Date: 2011-06-29 
  • Deposition Author(s): Xue, Y., Ha, Y.

Revision History  (Full details and data files)

  • Version 1.0: 2011-06-29
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2011-07-27
    Changes: Database references
  • Version 1.3: 2011-09-07
    Changes: Database references
  • Version 1.4: 2024-02-21
    Changes: Data collection, Database references, Derived calculations