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PDBsum entry 2ysz

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Protein binding PDB id
2ysz
Jmol
Contents
Protein chain
185 a.a. *
* Residue conservation analysis
PDB id:
2ysz
Name: Protein binding
Title: Solution structure of the chimera of thE C-terminal pid domain of fe65l and thE C-terminal tail peptide of app
Structure: Amyloid beta a4 precursor protein-binding family b member 2 and amyloid beta a4 protein. Chain: a. Fragment: pid domain and app peptide. Engineered: yes
Source: Mus musculus. Mouse. Organism_taxid: 10090. Other_details: cell-free protein synthesis
NMR struc: 20 models
Authors: H.Li,S.Koshiba,S.Watanabe,T.Harada,T.Kigawa,S.Yokoyama, Riken Structural Genomics/proteomics Initiative (Rsgi)
Key ref:
H.Li et al. (2008). 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. J Biol Chem, 283, 27165-27178. PubMed id: 18650440 DOI: 10.1074/jbc.M803892200
Date:
05-Apr-07     Release date:   08-Apr-08    
PROCHECK
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 Headers
 References

Protein chain
Pfam   ArchSchema ?
Q9DBR4  (APBB2_MOUSE) -  Amyloid beta A4 precursor protein-binding family B member 2
Seq:
Struc:
 
Seq:
Struc:
760 a.a.
185 a.a.*
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 59 residue positions (black crosses)

 

 
DOI no: 10.1074/jbc.M803892200 J Biol Chem 283:27165-27178 (2008)
PubMed id: 18650440  
 
 
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.
H.Li, S.Koshiba, F.Hayashi, N.Tochio, T.Tomizawa, T.Kasai, T.Yabuki, Y.Motoda, T.Harada, S.Watanabe, M.Inoue, Y.Hayashizaki, A.Tanaka, T.Kigawa, S.Yokoyama.
 
  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.
 
  Selected figure(s)  
 
Figure 2.
Structure of PID2 of Fe65L1 in its free form. The 20 PID2 conformers with the fewest violations (A) and the ribbon representation of PID2 (B) are shown in a side-by-side stereoformat. The secondary structures are shown in red and cyan for helices and sheets, respectively.
Figure 7.
Ribbon representation of the PID/PTB domains in complex with target peptides. PID2 of Fe65L1 is shown in green, and other PID/PTB domains are shown in light green. The target peptides are shown in magenta. In the target peptide, the NPX(p)Y motif, if it exists, is shown in cyan where the tyrosine or phosphorylated tyrosine residue is indicated, and the region forming the antiparallel β-sheet with the β5 strand of the PID/PTB domain is shown in red. A, Fe65L1 PID2 and APP peptide. B, X11 PTB domain and APP peptide. C, IRS-1 PTB domain and IL-4 peptide. D, Numb PTB domain and GPpY-containing peptide. E, SNT-1 PTB domain and fibroblast growth factor receptor 1 (FGFR1) peptide. The unique C-terminal β-strand of SNT-1 is shown in blue. F, Talin F3 domain and integrin peptide. The Protein Data Bank accession code for each complex is shown under each ribbon representation in parentheses.
 
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2008, 283, 27165-27178) copyright 2008.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20303980 M.Guttman, J.H.Prieto, T.M.Handel, P.J.Domaille, and E.A.Komives (2010).
Structure of the minimal interface between ApoE and LRP.
  J Mol Biol, 398, 306-319.
PDB codes: 2knx 2kny
20075861 M.J.Smith, W.R.Hardy, G.Y.Li, M.Goudreault, S.Hersch, P.Metalnikov, A.Starostine, T.Pawson, and M.Ikura (2010).
The PTB domain of ShcA couples receptor activation to the cytoskeletal regulator IQGAP1.
  EMBO J, 29, 884-896.  
20568118 O.Y.Kwon, K.Hwang, J.A.Kim, K.Kim, I.C.Kwon, H.K.Song, and H.Jeon (2010).
Dab1 binds to Fe65 and diminishes the effect of Fe65 or LRP1 on APP processing.
  J Cell Biochem, 111, 508-519.  
20213668 R.J.Falconer, A.Penkova, I.Jelesarov, and B.M.Collins (2010).
Survey of the year 2008: applications of isothermal titration calorimetry.
  J Mol Recognit, 23, 395-413.  
19656869 F.Diaz-Griffero, X.R.Qin, F.Hayashi, T.Kigawa, A.Finzi, Z.Sarnak, M.Lienlaf, S.Yokoyama, and J.Sodroski (2009).
A B-box 2 surface patch important for TRIM5alpha self-association, capsid binding avidity, and retrovirus restriction.
  J Virol, 83, 10737-10751.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.