The cytoplasmic domain of the β amyloid precursor protein (βAPP) may play a role in cellular events that lead to the secretion of the Aβ peptide, the major constituent of amyloid plaques found in the brains of individuals affected by Alzheimer's disease, by interacting with cellular factors involved in βAPP function or processing. In order to elucidate the structural basis of cytoplasmic domain activity, the conformations adopted in solution by a peptide containing the 47-residue C-terminal sequence of βAPP have been investigated by NMR and CD spectroscopy. The peptide does not have a stable tertiary structure, but local regions of the polypeptide chain populate defined conformations. In particular, the amino acid sequences TPEE and NPTY form type I reverse turns. These structured regions correspond to sequences within the cytoplasmic domain implicated in the biological activity of βAPP.
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