New structures help the modeling of toxic amyloidβ ion channels

The mechanism of amyloid toxicity is poorly understood and there are two schools of thought in this hotly debated field: the first favors membrane destabilization by intermediate-to-large amyloid oligomers, with consequent thinning and non-specific ion leakage; the second favors ion-specific permeable channels lined by small amyloid oligomers. Published results currently support both mechanisms. However, the amyloid beta (A beta) peptide has recently been shown to form a U-shaped 'beta-strand-turn-beta-strand' structure. This structure and the available physiological data present a challenge for computational biology - to provide candidate models consistent with the experimental data. Modeling based on small AP oligomers containing extramembranous N-termini predicts channels with shapes and dimensions consistent with experimentally derived channel structures. These results support the hypothesis that small A beta oligomers can form ion channels. Molecular dynamics modeling can provide blueprints of 3D structural conformations for many other amyloids whose membrane association is key to their toxicity.