Abstract
Neuronal Fe65 is a central adapter for the intracellular protein network of Alzheimer's disease related amyloid precursor protein (APP). It contains a unique tandem array of phosphotyrosine-binding (PTB) domains that recognize NPXY internalization motifs present in the intracellular domains of APP (AICD) and the low-density lipoprotein receptor-related protein LRP1 (LICD). The ternary APP/Fe65/LRP1 complex is an important mediator of APP processing and affects β-amyloid peptide production. Here we dissect by biochemical and biophysical methods the direct interactions within the ternary complex and reveal a phosphorylation-dependent insulin receptor substrate (IRS-) like interaction of the distal NPVY(4507) motif of LICD with Fe65-PTB1.
Copyright © 2011 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Alzheimer Disease / genetics
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Alzheimer Disease / metabolism*
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Amino Acid Motifs
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Amyloid beta-Protein Precursor / chemistry
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Amyloid beta-Protein Precursor / genetics
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Amyloid beta-Protein Precursor / metabolism*
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Humans
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Low Density Lipoprotein Receptor-Related Protein-1 / chemistry
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Low Density Lipoprotein Receptor-Related Protein-1 / genetics
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Low Density Lipoprotein Receptor-Related Protein-1 / metabolism*
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Multiprotein Complexes / chemistry
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Multiprotein Complexes / genetics
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Multiprotein Complexes / metabolism*
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Nerve Tissue Proteins / chemistry
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / metabolism*
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Nuclear Proteins / chemistry
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism*
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Protein Structure, Tertiary
Substances
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APBB1 protein, human
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APP protein, human
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Amyloid beta-Protein Precursor
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LRP1 protein, human
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Low Density Lipoprotein Receptor-Related Protein-1
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Multiprotein Complexes
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Nerve Tissue Proteins
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Nuclear Proteins