Molecular Dynamics Simulations of the Tau Amyloid Fibril Core Dimer at the Surface of a Lipid Bilayer Model: I. In Alzheimer's Disease

ABSTRACT: A tau R3???R4 domain spanning residues 306???378 was shown to form an amyloid fibril core of a full-length tau in the brain of patients with Alzheimer???s disease. Recently, we studied the dynamics of a tau R3???R4 monomer at the surface of a lipid bilayer model and revealed deep insertion of the amino acids spanning the PHF6 motif (residues 306???311) and its flanking residues. Here, we explore the membrane-associated conformational ensemble of a tau R3???R4 dimer by means of atomistic molecular dynamics. Similar to the monomer simulation, the R3???R4 dimer has the propensity to form fl-hairpin-like conformation. Unlike the monomer, the dimer shows insertion of the C-terminal R4 region and transient adsorption of the PHF6 motif. Taken together, these results reveal the multiplicity of adsorption and insertion modes of tau into membranes depending on its oligomer size.

Automated summary

The full-length tau protein in the brain of Alzheimer's disease patients has a amyloid fibril core formed by the R3-R4 domain. The study reveals that tau protein has multiple modes of adsorption and insertion into lipid bilayers, depending on its oligomer size.