Competition between Electrostatic and Hydrophobic Forces in the Central Core Region of Amyloid β Fibrils
Amyloidogenic peptides aggregated to large molecular assemblies are a hallmark of several diseases including Parkinson’s, Huntington’s, and Alzheimer’s disease as well as type II diabetes. Although each of these diseases gives rise to a very distinctive clinical picture, amyloid fibrils share the cross-β structure as a common structural motif. Within this motif, the peptide strands are linked via lateral β-sheet-turn-β-sheet structures that result in fiber-like aggregates with diameters of a few nanometers and lengths up to several micrometers.
The central question that will be addressed is how electrostatic and hydrophobic interactions compete within the central core region of Aβ(1-40) fibrils. By means of extensive molecular dynamics simulations we investigated a series of rationally mutated Aβ(1-40) variants, which feature charged side chains in the otherwise hydrophobic central core region of the fibril. Our study suggests considerable structural changes compared to wild type Aβ(1-40) fibrils that are consistent with parameters measured in solid-state NMR experiments.
Location: MLU, Von-Danckelmann-Platz 3, SR 1.09 Time: 3.30pm
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