Exploring Membrane Binding Targets of Disordered Human Tau Aggregates on Lipid Rafts Using Multiscale Molecular Dynamics Simulations.

ABSTRACT: The self-aggregation of tau, a microtubule-binding protein, has been linked to the onset of Alzheimer's Disease. Recent studies indicate that the disordered tau aggregates, or oligomers, are more toxic than the ordered fibrils found in the intracellular neurofibrillary tangles of tau. At present, details of tau oligomer interactions with lipid rafts, a model of neuronal membranes, are not known. Using molecular dynamics simulations, the lipid-binding events, membrane-damage, and protein folding of tau oligomers on various lipid raft surfaces were investigated. Tau oligomers preferred to bind to the boundary domains (Lod) created by the coexisting liquid-ordered (Lo) and liquid-disordered (Ld) domains in the lipid rafts. Additionally, stronger binding of tau oligomers to the ganglioside (GM

SUBMITTER: Cheng KH 

PROVIDER: S-EPMC9695534 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature