Study of the Conformational Transition of A(1-42) Using D-Amino Acid Replacement Analogues
详细信息 查看全文
- 作者：Katharina Janek ; Sven Rothemund ; Klaus Gast ; Michael Beyermann ; Josef Zipper ; Heinz Fabian ; Michael Bienert ; and Eberhard Krause
- 刊名：Biochemistry
- 出版年：2001
- 出版时间：May 8, 2001
- 年：2001
- 卷：40
- 期：18
- 页码：5457 - 5463
- 全文大小：169K
- 年卷期：v.40,no.18(May 8, 2001)
- ISSN：1520-4995
文摘
A critical event in Alzheimer's disease is the transition of A
peptides from their solubleforms into disease-associated -sheet-rich conformers. Structural analysis of a complete D-amino acidreplacement set of A(1-42) enabled us to localize in the full-length 42-mer peptide the region responsiblefor the conformational switch into a -sheet structure. Although NMR spectroscopy of trifluoroethanol-stabilized monomeric A(1-42) delineated two separated helical domains, only the destabilization ofhelix I, comprising residues 11-24, caused a transition to a -sheet structure. This conformational 
-to-switch was directly accompanied by an aggregation process leading to the formation of amyloid fibrils.
peptides from their solubleforms into disease-associated -sheet-rich conformers. Structural analysis of a complete D-amino acidreplacement set of A(1-42) enabled us to localize in the full-length 42-mer peptide the region responsiblefor the conformational switch into a -sheet structure. Although NMR spectroscopy of trifluoroethanol-stabilized monomeric A(1-42) delineated two separated helical domains, only the destabilization ofhelix I, comprising residues 11-24, caused a transition to a -sheet structure. This conformational -to-switch was directly accompanied by an aggregation process leading to the formation of amyloid fibrils.