Identification, transmembrane orientation and biogenesis of the amyloid A4 precursor of Alzheimer's disease.
The precursor of the Alzheimer's disease-specific amyloid A4 protein is an integral, glycosylated membrane protein which spans the bilayer once. The carboxy-terminal domain of 47 residues was located at the cytoplasmic site of the membrane. The three domains following the transient signal sequence of 17 residues face the opposite side of the membrane. The C-terminal 100 residues of the precursor comprising the amyloid A4 part and the cytoplasmic domain have a high tendency to aggregate, and proteinase K treatment results in peptides of the size of amyloid A4. This finding suggests that there is a precursor-product relationship between precursor and amyloid A4 and we conclude that besides proteolytic cleavage other events such as post-translational modification and membrane injury are primary events that precede the release of the small aggregating amyloid A4 subunit.
D000544:Alzheimer Disease / Q000378:metabolism*; D000595:Amino Acid Sequence; D000682:Amyloid / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor; D001483:Base Sequence; D002462:Cell Membrane / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism*; D008969:Molecular Sequence Data; D014176:Protein Biosynthesis; D011498:Protein Precursors / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000235:genetics*; D014158:Transcription, Genetic
D000682:Amyloid; D016564:Amyloid beta-Protein Precursor; D008562:Membrane Glycoproteins; D011498:Protein Precursors; D011956:Receptors, Cell Surface