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PDBsum entry 2yt1
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Protein binding
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PDB id
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2yt1
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References listed in PDB file
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Key reference
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Title
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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.
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Authors
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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.
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Ref.
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J Biol Chem, 2008,
283,
27165-27178.
[DOI no: ]
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PubMed id
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Abstract
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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.
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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.
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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.
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The above figures are
reprinted
by permission from the ASBMB:
J Biol Chem
(2008,
283,
27165-27178)
copyright 2008.
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