1WGU

Solution Structure of the C-terminal Phosphotyrosine Interaction Domain of APBB2 from Mouse

Summary for 1WGU

• Entry DOI: 10.2210/pdb1wgu/pdb
• NMR Information: BMRB: 10235
• Descriptor: amyloid beta (A4) precursor protein-binding, family B, member 2 (1 entity in total)
• Functional Keywords: phosphotyrosine-interaction domain, amyloid disease, structural genomics, riken structural genomics/proteomics initiative, rsgi, protein binding
• Biological source: Mus musculus (house mouse)
• Total number of polymer chains: 1
• Total formula weight: 14750.55

Authors

Li, H.,Hayashi, F.,Koshiba, S.,Inoue, M.,Kigawa, T.,Yokoyama, S.,RIKEN Structural Genomics/Proteomics Initiative (RSGI) (deposition date: 2004-05-28, release date: 2004-11-28, 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