Open AccessSolution Structure and Peptide Binding of the PTB Domain from the AIDA1 Postsynaptic Signaling Scaffolding Protein
Author(s) -
Ekaterina Smirnova,
Riya Shanbhag,
Arwa Kurabi,
Mehdi Mobli,
Jamie J. Kwan,
Logan W. Donaldson
Publication year - 2013
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0065605
Subject(s) - scaffold protein , postsynaptic density , peptide , microbiology and biotechnology , binding domain , peptide sequence , plasma protein binding , protein domain , biology , amyloid precursor protein , computational biology , signal transduction , postsynaptic potential , chemistry , binding site , biochemistry , gene , receptor , alzheimer's disease , disease , medicine , pathology
AIDA1 links persistent chemical signaling events occurring at the neuronal synapse with global changes in gene expression. Consistent with its role as a scaffolding protein, AIDA1 is composed of several protein-protein interaction domains. Here we report the NMR structure of the carboxy terminally located phosphotyrosine binding domain (PTB) that is common to all AIDA1 splice variants. A comprehensive survey of peptides identified a consensus sequence around an NxxY motif that is shared by a number of related neuronal signaling proteins. Using peptide arrays and fluorescence based assays, we determined that the AIDA1 PTB domain binds amyloid protein precursor (APP) in a similar manner to the X11/Mint PTB domain, albeit at reduced affinity (∼10 µM) that may allow AIDA1 to effectively sample APP, as well as other protein partners in a variety of cellular contexts.
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