PDBsum entry 2yt1

Protein binding

PDB id: 2yt1

Contents

Protein chain

185 a.a. *

* Residue conservation analysis

PDB id:

2yt1

Name:

Protein binding

Title:

Solution structure of the chimera of thE C-terminal tail peptide of app and thE C-terminal pid domain of fe65l

Structure:

Amyloid beta a4 protein and amyloid beta a4 precursor protein-binding family b member 2. Chain: a. Fragment: app peptide and pid domain. 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

Protein chain

Q9DBR4  (APBB2_MOUSE) -  Amyloid beta precursor protein binding family B member 2 from Mus musculus

Seq: 760 a.a.

Struc: 185 a.a.*

* PDB and UniProt seqs differ at 60 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.?

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.