Polymorphism of Alzheimer's Abeta17-42 (p3) oligomers: the importance of the turn location and its conformation.

ABSTRACT: Abeta(17-42) (so-called p3) amyloid is detected in vivo in the brains of individuals with Alzheimer's disease or Down's syndrome. We investigated the polymorphism of Abeta(17-42) oligomers based on experimental data from steady-state NMR measurements, electron microscopy, two-dimensional hydrogen exchange, and mutational studies, using all-atom molecular-dynamics simulation with explicit solvent. We assessed the structural stability and the populations. Our results suggest that conformational differences in the U-turn of Abeta(17-42) lead to polymorphism in beta-sheet registration and retention of an ordered beta-strand organization at the termini. Further, although the parallel Abeta(17-42) oligomer organization is the most stable of the conformers investigated here, different antiparalle

SUBMITTER: Miller Y 

PROVIDER: S-EPMC2726324 | biostudies-literature | 2009 Aug

REPOSITORIES: biostudies-literature