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PDBsum entry 5nqh
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Signaling protein
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PDB id
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5nqh
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PDB id:
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| Name: |
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Signaling protein
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Title:
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Structure of the human fe65-ptb2 homodimer
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Structure:
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Amyloid beta a4 precursor protein-binding family b member 1. Chain: a, b, c, d. Synonym: protein fe65. Engineered: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: apbb1, fe65, rir. Expressed in: escherichia coli. Expression_system_taxid: 562
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Resolution:
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2.60Å
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R-factor:
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0.195
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R-free:
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0.241
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Authors:
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L.P.Feilen,K.Haubrich,I.Sinning,U.Konietzko,S.Kins,B.Simon,K.Wild
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Key ref:
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L.P.Feilen
et al.
(2017).
Fe65-PTB2 Dimerization Mimics Fe65-APP Interaction.
Front Mol Neurosci,
10,
140.
PubMed id:
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Date:
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20-Apr-17
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Release date:
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03-May-17
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PROCHECK
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Headers
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References
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O00213
(APBB1_HUMAN) -
Amyloid beta precursor protein binding family B member 1 from Homo sapiens
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Seq:
Struc:
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710 a.a.
128 a.a.
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Key: |
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PfamA domain |
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Secondary structure |
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Front Mol Neurosci
10:140
(2017)
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PubMed id:
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Fe65-PTB2 Dimerization Mimics Fe65-APP Interaction.
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L.P.Feilen,
K.Haubrich,
P.Strecker,
S.Probst,
S.Eggert,
G.Stier,
I.Sinning,
U.Konietzko,
S.Kins,
B.Simon,
K.Wild.
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ABSTRACT
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Physiological function and pathology of the Alzheimer's disease causing amyloid
precursor protein (APP) are correlated with its cytosolic adaptor Fe65
encompassing a WW and two phosphotyrosine-binding domains (PTBs). The C-terminal
Fe65-PTB2 binds a large portion of the APP intracellular domain (AICD) including
the GYENPTY internalization sequence fingerprint. AICD binding to Fe65-PTB2
opens an intra-molecular interaction causing a structural change and altering
Fe65 activity. Here we show that in the absence of the AICD, Fe65-PTB2 forms a
homodimer in solution and determine its crystal structure at 2.6 Å resolution.
Dimerization involves the unwinding of a C-terminal α-helix that mimics binding
of the AICD internalization sequence, thus shielding the hydrophobic binding
pocket. Specific dimer formation is validated by nuclear magnetic resonance
(NMR) techniques and cell-based analyses reveal that Fe65-PTB2 together with the
WW domain are necessary and sufficient for dimerization. Together, our data
demonstrate that Fe65 dimerizes via its APP interaction site, suggesting that
besides intra- also intermolecular interactions between Fe65 molecules
contribute to homeostatic regulation of APP mediated signaling.
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