Dependence of the Formation of Tau and A? Peptide Mixed Aggregates on the Secondary Structure of the N-Terminal Region of A?.

ABSTRACT: One of the hallmarks of Alzheimer's disease is the formation of aggregates of the tau protein, a process that can be facilitated by the presence of fibrils formed by the amyloid ? peptide (A?). However, the mechanism that triggers tau aggregation is still a matter of debate. The effect of A?40 fibrils on the aggregation of the repeat domain of tau (TauRD) is investigated here by employing coarse-grained molecular dynamics simulations. The results indicate that the repeat domain of tau has a high affinity for A?40 fibrils, with the 261GSTENLK267 fragment of tau driving TauRD toward the 16KLVFFA21 fragment in A?40. Monomeric A?40, in which the 16KLVFFA21 fragment is rarely found in an extended conformation (as in the fibril), has a low affinity for the TauRD, indicating that the ability of A?40 fibrils to bind to the TauRD depends on the 16KLVFFA21 fragment of A? adopting an extended conformation.

SUBMITTER: Rojas AV 

PROVIDER: S-EPMC6524542 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature