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

Bulletin of the Korean chemical society

Dongha Baek¹  Song Yub Shin¹  Dong-Il Kang¹  Yangmee Kim¹ 

关键词: Alzheimer¡¯s disease;    APP;    CT26;    NMR spectroscopy;    CD spectroscopy;   

DOI  :  

学科分类：化学（综合）

来源: Korean Chemical Society

【 摘 要 】

C-terminal fragments of APP (APP-CTs), that contain A�? 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 �?-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 �?-helical structure from Val² to Lys¹¹ in TFE-containing aqueous solution. However, according to CD data, CT26 adopts a �?-sheet structure in the SDS micelles and DPC micelles. This result implies that CT26 may have a conformational transition between �?-helix and �?-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.

【 授权许可】

Unknown