Structure of CT26 in the C-terminal of Amyloid Precursor Protein Studied by NMR Spectroscopy

C-terminal fragments of APP (APP-CTs), that contain A$\beta$ sequence, are found in neurotic plaques, neurofibrillary tangles and the cytosol of lymphoblastoid cells obtained from AD patients. CT26, Thr639-Asp664 (TVIVITLVMLKKKQYTSIHH GVVEVD) includes not only the transmembrane domain but also the cytoplasmic domain of APP. This sequence is produced from cleavage of APP by caspase and $\gamma$-secretase. In this study, the solution structure of CT26 was investigated using NMR spectroscopy and circular dichroism (CD) spectropolarimeter in various membrane-mimicking environments. According to CD spectra and the tertiary structure of CT26 determined in TFE-containing aqueous solution, CT26 has an α-helical structure from $Val^{2}\;to\;Lys^{11}$ in TFE-containing aqueous solution. However, according to CD data, CT26 adopts a $\beta$-sheet structure in the SDS micelles and DPC micelles. This result implies that CT26 may have a conformational transition between $\alpha$-helix and $\beta$-sheet structure. This study may provide an insight into the conformational basis of the pathological activity of the C-terminal fragments of APP in the model membrane.