Monomer adds to preformed structured oligomers of Abeta-peptides by a two-stage dock-lock mechanism.

ABSTRACT: Nonfibrillar soluble oligomers, which are intermediates in the transition from monomers to amyloid fibrils, may be the toxic species in Alzheimer's disease. To monitor the early events that direct assembly of amyloidogenic peptides we probe the dynamics of formation of (Abeta(16-22))(n) by adding a monomer to a preformed (Abeta(16-22))(n-1) (n = 4-6) oligomer in which the peptides are arranged in an antiparallel beta-sheet conformation. All atom molecular dynamics simulations in water and multiple long trajectories, for a cumulative time of 6.9 mus, show that the oligomer grows by a two-stage dock-lock mechanism. The largest conformational change in the added disordered monomer occurs during the rapid ( approximately 50 ns) first dock stage in which the beta-strand content of the monomer i

SUBMITTER: Nguyen PH 

PROVIDER: S-EPMC1766316 | biostudies-literature | 2007 Jan

REPOSITORIES: biostudies-literature