Back to Search
Start Over
A 127-kDa protein (UV-DDB) binds to the cytoplasmic domain of the Alzheimer's amyloid precursor protein
- Source :
- Journal of neurochemistry. 72(2)
- Publication Year :
- 1999
-
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.
- Subjects :
- Cytoplasm
DNA Repair
Amyloid beta
Ultraviolet Rays
Recombinant Fusion Proteins
Molecular Sequence Data
Peptide
Biochemistry
PC12 Cells
Electron Transport Complex IV
Cellular and Molecular Neuroscience
Amyloid beta-Protein Precursor
Alzheimer Disease
mental disorders
Amyloid precursor protein
Animals
Humans
Amino Acid Sequence
Integral membrane protein
chemistry.chemical_classification
biology
Escherichia coli Proteins
P3 peptide
Haplorhini
Fusion protein
Precipitin Tests
Protein Structure, Tertiary
Rats
DNA-Binding Proteins
Alpha secretase
chemistry
biology.protein
Rabbits
Amyloid precursor protein secretase
Bacterial Outer Membrane Proteins
DNA Damage
Protein Binding
Subjects
Details
- ISSN :
- 00223042
- Volume :
- 72
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Journal of neurochemistry
- Accession number :
- edsair.doi.dedup.....a96e970407c163d248098b1f718c4eff