PDBsum entry: 2roz

Peptide binding protein

PDB-id: 2roz

Contents

Description

Header details

Header records

References

PROCHECK

Protein chains

32 a.a. *

136 a.a. *

* Residue conservation analysis

Tools

Clefts Calculation

PDB id:

2roz

Name:

Peptide binding protein

Title:

Structure of thE C-terminal pid domain of fe65l1 complexed with the cytoplasmic tail of app reveals a novel peptide binding mode

Structure:

Peptide from amyloid beta a4 protein. Chain: a. Synonym: app-derived_32-mer_peptide. Engineered: yes. Amyloid beta a4 precursor protein-binding family b member 2. Chain: b. Fragment: c-terminal pid domain. Synonym: fe65l1.

Source:

Synthetic: yes. Other_details: chemical synthesis. Mus musculus. Mouse. Organism_taxid: 10090. Gene: apbb2. Expressed in: cell-free synthesis. Other_details: e. Coli cell-free

UniProt:

Chain A: P12023 (A4_MOUSE)

Seq:
Struc:
	Seq:
	Struc:
Seq:
Struc:
	Seq:	770 a.a.
	Struc:	32 a.a.

Chain B: Q9DBR4 (APBB2_MOUSE)

Seq:

Struc:

Seq:

Struc:

Seq:

760 a.a.

Struc:

136 a.a.*

Key:

PfamA domain

Secondary structure

* PDB and UniProt seqs differ at 13 residue positions (black crosses)

Resolution:

not givenÅ

NMR structure:

20 models

Authors:

H.Li,S.Koshiba,N.Tochio,S.Watanabe,T.Harada,M.Inoue, 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:

25-Apr-08

Release date:

22-Jul-08

Quick_links

Procheck

Clefts

Surface

Key reference

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 the author.