Amino acid substitutions [K16A] and [K28A] distinctly affect amyloid β-protein oligomerization.

ABSTRACT: Amyloid β-protein (A β) assembles into oligomers that play a seminal role in Alzheimer's disease (AD), a leading cause of dementia among the elderly. Despite undisputed importance of A β oligomers, their structure and the basis of their toxicity remain elusive. Previous experimental studies revealed that the [K16A] substitution strongly inhibits toxicity of the two predominant A β alloforms in the brain, A β 40 and A β 42, whereas the [K28A] substitution exerts only a moderate effect. Here, folding and oligomerization of [A16]A β 40, [A28]A β 40, [A16]A β 42, and [A28]A β 42 are examined by discrete molecular dynamics (DMD) combined with a four-bead implicit solvent force field, DMD4B-HYDRA, and compared to A β 40 and A β 42 oligomer formation. Our results show that both substitutions prom

SUBMITTER: Zganec M 

PROVIDER: S-EPMC4942424 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature