A selectivity filter at the intracellular end of the acid-sensing ion channel pore

Research output: Contribution to journalJournal articlepeer-review

Documents

  • Timothy Lynagh
  • Emelie Flood
  • Céline Boiteux
  • Matthias Wulf
  • Vitaly V Komnatnyy
  • Janne M Colding
  • Toby W Allen
  • Pless, Stephan

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.

Original languageEnglish
Article number24630
JournaleLife
Volume6
Number of pages21
ISSN2050-084X
DOIs
Publication statusPublished - 12 May 2017

    Research areas

  • Journal Article

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