Study of the conformational transition of Aβ(1-42) using D-amino acid replacement analogues
Study of the conformational transition of Aβ(1-42) using D-amino acid replacement analogues
复制标题
DOI：
10.1021/bi002005e
复制
发表时间：
2001-05-08
期刊：
影响因子：
2.9
通讯作者：
Krause, E
中科院分区：
文献类型：
--
作者：
Janek, K;Rothemund, S;Krause, E
阿尔茨海默病中的关键事件是A β肽从其可溶形式转变为疾病相关的富含β-片层的构象异构体。A β（1-42）的完整D-氨基酸置换组的结构分析使我们能够在全长42-mer肽中定位负责构象转换成β-折叠结构的区域。尽管三氟乙醇稳定的单体A β（1-42）的NMR光谱描绘了两个分离的螺旋结构域，但只有包含残基11-24的螺旋I的去稳定化引起向β-折叠结构的转变。这种构象α到β的转换直接伴随着导致淀粉样蛋白原纤维形成的聚集过程。
A critical event in Alzheimer's disease is the transition of A beta peptides from their soluble forms into disease-associated beta -sheet-rich conformers. Structural analysis of a complete D-amino acid replacement set of A beta (1-42) enabled us to localize in the full-length 42-mer peptide the region responsible for the conformational switch into a beta -sheet structure. Although NMR spectroscopy of trifluoroethanol-stabilized monomeric A beta (1-42) delineated two separated helical domains, only the destabilization of helix I, comprising residues 11-24, caused a transition to a beta -sheet structure. This conformational alpha -to-beta switch was directly accompanied by an aggregation process leading to the formation of amyloid fibrils.