2ROZ

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

Summary for 2ROZ

• Entry DOI: 10.2210/pdb2roz/pdb
• NMR Information: BMRB: 10236
• Descriptor: peptide from Amyloid beta A4 protein, Amyloid beta A4 precursor protein-binding family B member 2 (2 entities in total)
• Functional Keywords: fe65l1, pid domain, amyloid precursor protein, alternative splicing, amyloid, apoptosis, cell adhesion, coated pit, copper, endocytosis, glycoprotein, heparin-binding, iron, membrane, metal-binding, notch signaling pathway, phosphoprotein, protease inhibitor, serine protease inhibitor, transmembrane, zinc, structural genomics, nppsfa, national project on protein structural and functional analyses, riken structural genomics/proteomics initiative, rsgi, peptide binding protein
• Biological source: Mus musculus (mouse); More
• Cellular location: Membrane; Single-pass type I membrane protein: P12023
• Total number of polymer chains: 2
• Total formula weight: 18586.73

Authors

Li, H.,Koshiba, S.,Tochio, N.,Watanabe, S.,Harada, T.,Inoue, M.,Kigawa, T.,Yokoyama, S.,RIKEN Structural Genomics/Proteomics Initiative (RSGI) (deposition date: 2008-04-25, release date: 2008-07-22, Last modification date: 2024-05-29)

Primary citation

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.
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, 2008

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.

PubMed: 18650440
DOI: 10.1074/jbc.M803892200

Experimental method

SOLUTION NMR