A 127-kDa protein (UV-DDB) binds to the cytoplasmic domain of the Alzheimer's amyloid precursor protein

J Neurochem. 1999 Feb;72(2):549-56. doi: 10.1046/j.1471-4159.1999.0720549.x.

Abstract

Alzheimer amyloid precursor protein (APP) is an integral membrane protein with a short cytoplasmic domain of 47 amino acids. It is hoped that identification of proteins that interact with the cytoplasmic domain will provide new insights into the physiological function of APP and, in turn, into the pathogenesis of Alzheimer's disease. To identify proteins that interact with the cytoplasmic domain of APP, we employed affinity chromatography using an immobilized synthetic peptide corresponding to residues 645-694 of APP695 and identified a protein of approximately 130 kDa in rat brain cytosol. Amino acid sequencing of the protein revealed the protein to be a rat homologue of monkey UV-DDB (UV-damaged DNA-binding protein, calculated molecular mass of 127 kDa). UV-DDB/p127 co-immunoprecipitated with APP using an anti-APP antibody from PC12 cell lysates. APP also co-immunoprecipitated with UV-DDB/p127 using an anti-UV-DDB/p127 antibody. These results indicate that UV-DDB/p127, which is present in the cytosolic fraction, forms a complex with APP through its cytoplasmic domain. In vitro binding experiments using a glutathione S-transferase-APP cytoplasmic domain fusion protein and several mutants indicated that the YENPTY motif within the APP cytoplasmic domain, which is important in the internalization of APP and amyloid beta protein secretion, may be involved in the interaction between UV-DDB/p127 and APP.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alzheimer Disease / metabolism*
  • Amino Acid Sequence
  • Amyloid beta-Protein Precursor / chemistry
  • Amyloid beta-Protein Precursor / metabolism*
  • Animals
  • Bacterial Outer Membrane Proteins / metabolism
  • Cytoplasm / enzymology
  • DNA Damage*
  • DNA Repair*
  • DNA-Binding Proteins / metabolism*
  • DNA-Binding Proteins / radiation effects
  • Electron Transport Complex IV / metabolism
  • Escherichia coli Proteins*
  • Haplorhini
  • Humans
  • Molecular Sequence Data
  • PC12 Cells
  • Precipitin Tests
  • Protein Binding / physiology
  • Protein Binding / radiation effects
  • Protein Structure, Tertiary
  • Rabbits
  • Rats
  • Recombinant Fusion Proteins / metabolism
  • Ultraviolet Rays

Substances

  • Amyloid beta-Protein Precursor
  • Bacterial Outer Membrane Proteins
  • DNA-Binding Proteins
  • Escherichia coli Proteins
  • Recombinant Fusion Proteins
  • CbdA protein, E coli
  • Electron Transport Complex IV