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Molecular Mechanism of Anion Permeation Through Aquaporin 6 by Yamamoto, Eiji; Joo, Keehyoung; Lee, Jooyoung; Sansom, Mark S. P.; Yasui, Masato is a scholarly article available to read on EtoBox.

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Aquaporins (AQPs) are recognized as transmembrane water channels that facilitate selective water permeation through their monomeric pores. Among the AQP family, AQP6 has a unique characteristic as an anion channel, which is allosterically controlled by pH conditions and is eliminated by a single amino acid mutation. However, the molecular mechanism of anion permeation through AQP6 remains unclear. Using molecular dynamics simulations in the presence of a transmembrane voltage utilizing an ion concentration gradient, we show that chloride ions permeate through the pore corresponding to the central axis of the AQP6 homotetramer. Under low pH conditions, a subtle opening of the hydrophobic selective filter (SF), located near the extracellular part of the central pore, becomes wetted and enables anion permeation. Our simulations also indicate that a single mutation (N63G) in human AQP6, located at the central pore, significantly reduces anion conduction, consistent with experimental data. Moreover, we demonstrate the pH-sensing mechanism in which the protonation of H184 and H189 under low pH conditions allosterically triggers the gating of the SF region. These results suggest a unique

Author

Yamamoto, Eiji; Joo, Keehyoung; Lee, Jooyoung; Sansom, Mark S. P.; Yasui, Masato

Published

2023

Language

EN