title: Phosphorylation of LRP1 regulates the interaction with Fe65.
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.
authors.affiliation: Heidelberg University Biochemistry Center (BZH), Heidelberg, Germany.
authors.forename: Wilfried
authors.initials: W
authors.lastname: Klug
authors.forename: Andreas
authors.initials: A
authors.lastname: Dietl
authors.forename: Bernd
authors.initials: B
authors.lastname: Simon
authors.forename: Irmgard
authors.initials: I
authors.lastname: Sinning
authors.forename: Klemens
authors.initials: K
authors.lastname: Wild
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism*; D020816:Amino Acid Motifs; D016564:Amyloid beta-Protein Precursor / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D026503:Low Density Lipoprotein Receptor-Related Protein-1 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D046912:Multiprotein Complexes / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary
chemical_list: C091042:APBB1 protein, human; C545487:APP protein, human; D016564:Amyloid beta-Protein Precursor; C475476:LRP1 protein, human; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D046912:Multiprotein Complexes; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins