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

Archive ouverte

Nguyen, Phuong, H | Derreumaux, Philippe

Edité par CCSD ; American Chemical Society -

International audience. The tau R3-R4 domain spanning residues 306-378 was shown to form the amyloid fibril core of full-length tau in the brain of patient with Alzheimer's disease. Recently, we studied the dynamics of 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 tau R3-R4 dimer by means of atomistic molecular dynamics. Similar to the monomer simulation, R3-R4 dimer has the propensity to form β-hairpin-like conformation. Unlike the monomer, the dimer shows deep 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.

• Description
• Sujet/Public
• Outil
• Outil d'anticipation
• Mémoire et thèse
• Gestion