2ROZ

Structure of the C-terminal PID Domain of Fe65L1 Complexed with the Cytoplasmic Tail of APP Reveals a Novel Peptide Binding Mode


Experimental Data Snapshot

  • Method: SOLUTION NMR
  • Conformers Calculated: 100 
  • Conformers Submitted: 20 
  • Selection Criteria: target function 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Structure of the C-terminal phosphotyrosine interaction domain of Fe65L1 complexed with the cytoplasmic tail of amyloid precursor protein reveals a novel peptide binding mode

Li, H.Koshiba, S.Hayashi, F.Tochio, N.Tomizawa, T.Kasai, T.Yabuki, T.Motoda, Y.Harada, T.Watanabe, S.Inoue, M.Hayashizaki, Y.Tanaka, A.Kigawa, T.Yokoyama, S.

(2008) J Biol Chem 283: 27165-27178

  • DOI: https://doi.org/10.1074/jbc.M803892200
  • Primary Citation of Related Structures:  
    1WGU, 2ROZ, 2YSZ, 2YT0, 2YT1

  • PubMed Abstract: 

    Fe65L1, a member of the Fe65 family, is an adaptor protein that interacts with the cytoplasmic domain of Alzheimer amyloid precursor protein (APP) through its C-terminal phosphotyrosine interaction/phosphotyrosine binding (PID/PTB) domain. In the present study, the solution structures of the C-terminal PID domain of mouse Fe65L1, alone and in complex with a 32-mer peptide (DAAVTPEERHLSKMQQNGYENPTYKFFEQMQN) derived from the cytoplasmic domain of APP, were determined using NMR spectroscopy. The C-terminal PID domain of Fe65L1 alone exhibits a canonical PID/PTB fold, whereas the complex structure reveals a novel mode of peptide binding. In the complex structure, the NPTY motif forms a type-I beta-turn, and the residues immediately N-terminal to the NPTY motif form an antiparallel beta-sheet with the beta5 strand of the PID domain, the binding mode typically observed in the PID/PTB.peptide complex. On the other hand, the N-terminal region of the peptide forms a 2.5-turn alpha-helix and interacts extensively with the C-terminal alpha-helix and the peripheral regions of the PID domain, representing a novel mode of peptide binding that has not been reported previously for the PID/PTB.peptide complex. The indispensability of the N-terminal region of the peptide for the high affinity of the PID-peptide interaction is consistent with NMR titration and isothermal calorimetry data. The extensive binding features of the PID domain of Fe65L1 with the cytoplasmic domain of APP provide a framework for further understanding of the function, trafficking, and processing of APP modulated by adapter proteins.


  • Organizational Affiliation

    Systems and Structural Biology Center, RIKEN Yokohama Institute, 1-7-22 Suehiro-cho, Tsurumi, Yokohama 230-0045, Japan.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
peptide from Amyloid beta A4 protein32N/AMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for P12023 (Mus musculus)
Explore P12023 
Go to UniProtKB:  P12023
IMPC:  MGI:88059
Entity Groups  
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UniProt GroupP12023
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 precursor protein-binding family B member 2136Mus musculusMutation(s): 0 
Gene Names: Apbb2
UniProt & NIH Common Fund Data Resources
Find proteins for Q9DBR4 (Mus musculus)
Explore Q9DBR4 
Go to UniProtKB:  Q9DBR4
IMPC:  MGI:108405
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ9DBR4
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: SOLUTION NMR
  • Conformers Calculated: 100 
  • Conformers Submitted: 20 
  • Selection Criteria: target function 

Structure Validation

View Full Validation Report



Entry History 

Revision History  (Full details and data files)

  • Version 1.0: 2008-07-22
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2022-03-16
    Changes: Data collection, Database references, Derived calculations
  • Version 1.3: 2024-05-29
    Changes: Data collection