1M7E

Crystal structure of the phosphotyrosine binding domain(PTB) of mouse Disabled 2(Dab2):implications for Reeling signaling


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.45 Å
  • R-Value Free: 0.273 
  • R-Value Work: 0.244 

wwPDB Validation   3D Report Full Report


This is version 1.4 of the entry. See complete history


Literature

Crystal structures of the Dab homology domains of mouse disabled 1 and 2

Yun, M.Keshvara, L.Park, C.-G.Zhang, Y.-M.Dickerson, J.B.Zheng, J.Rock, C.O.Curran, T.Park, H.-W.

(2003) J Biol Chem 278: 36572-36581

  • DOI: https://doi.org/10.1074/jbc.M304384200
  • Primary Citation of Related Structures:  
    1M7E, 1OQN, 1P3R

  • PubMed Abstract: 

    Disabled (Dab) 1 and 2 are mammalian homologues of Drosophila DAB. Dab1 is a key cytoplasmic mediator in Reelin signaling that controls cell positioning in the developing central nervous system, whereas Dab2 is an adapter protein that plays a role in endocytosis. DAB family proteins possess an amino-terminal DAB homology (DH) domain that is similar to the phosphotyrosine binding/phosphotyrosine interaction (PTB/PI) domain. We have solved the structures of the DH domains of Dab2 (Dab2-DH) and Dab1 (Dab1-DH) in three different ligand forms, ligand-free Dab2-DH, the binary complex of Dab2-DH with the Asn-Pro-X-Tyr (NPXY) peptide of amyloid precursor protein (APP), and the ternary complex of Dab1-DH with the APP peptide and inositol 1,4,5-trisphosphate (Ins-1,4,5-P3, the head group of phosphatidylinositol-4,5-diphosphate (PtdIns-4,5-P2)). The similarity of these structures suggests that the rigid Dab DH domain maintains two independent pockets for binding of the APP/lipoprotein receptors and phosphoinositides. Mutagenesis confirmed the structural determinants specific for the NPXY sequence and PtdIns-4,5-P2 binding. NMR spectroscopy confirmed that the DH domain binds to Ins-1,4,5-P3 independent of the NPXY peptides. These findings suggest that simultaneous interaction of the rigid DH domain with the NPXY sequence and PtdIns-4,5-P2 plays a role in the attachment of Dab proteins to the APP/lipoprotein receptors and phosphoinositide-rich membranes.


  • Organizational Affiliation

    Department of Structural Biology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105-2794, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Disabled homolog 2
A, B, C
160Mus musculusMutation(s): 0 
UniProt
Find proteins for P98078 (Mus musculus)
Explore P98078 
Go to UniProtKB:  P98078
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP98078
Sequence Annotations
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  • Reference Sequence

Find similar proteins by:  Sequence   |   3D Structure  

Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
NGYENPTYK peptide
D, E, F
9N/AMutation(s): 0 
UniProt
Find proteins for P08592 (Rattus norvegicus)
Explore P08592 
Go to UniProtKB:  P08592
Entity Groups  
UniProt GroupP08592
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.45 Å
  • R-Value Free: 0.273 
  • R-Value Work: 0.244 
  • Space Group: H 3 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 127.258α = 90
b = 127.258β = 90
c = 269.541γ = 120
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
CNSrefinement
CNSphasing

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2003-08-05
    Type: Initial release
  • Version 1.1: 2008-04-28
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2022-12-21
    Changes: Database references
  • Version 1.4: 2024-05-22
    Changes: Data collection