A Selectivity Filter at the Intracellular End of the Acid-sensing Ion Channel Pore

Overview

Journal Elife

Specialty Biology

Date 2017 May 13

PMID 28498103

Citations 30

Authors

Timothy Lynagh

Emelie Flood

Celine Boiteux

Matthias Wulf

Vitaly V Komnatnyy

Janne M Colding

Toby W Allen

Stephan A Pless

Affiliations

Soon will be listed here.

Abstract

Increased extracellular proton concentrations during neurotransmission are converted to excitatory sodium influx by acid-sensing ion channels (ASICs). 10-fold sodium/potassium selectivity in ASICs has long been attributed to a central constriction in the channel pore, but experimental verification is lacking due to the sensitivity of this structure to conventional manipulations. Here, we explored the basis for ion selectivity by incorporating unnatural amino acids into the channel, engineering channel stoichiometry and performing free energy simulations. We observed no preference for sodium at the "GAS belt" in the central constriction. Instead, we identified a band of glutamate and aspartate side chains at the lower end of the pore that enables preferential sodium conduction.

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