The structure of tyrosine-10 favors ionic conductance of Alzheimer’s disease-associated full-length amyloid-β channels

Membrane channel forming activities of the peptides

Voltage clamp experiments have been conducted at selected hold voltages between +100 mV and −100 mV (the sign corresponds to the trans side, where the peptide was added). At +50 mV transmembrane voltage, the current reached a baseline level of ~40 pA at ~5 min following addition of Aβ_1-42, featuring stepwise transitions between discrete conductance levels (Fig. 1a). The stability of the conductance pattern and the consistent amplitude of the transitions suggest that Aβ_1-42 inserts into the membrane and forms ion-conducting channels that are able to switch between on/off states.

Aβ_1-42 (a), Aβ_1-40 (b), AβpE_3-42 (c), and AβpE_3-40 (d) at 50 mV membrane-hold potential in 1 M KCl + 10 mM HEPES buffer, pH 7.4. The membranes were composed of…