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

Research output: Contribution to journalJournal articleResearchpeer-review

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A selectivity filter at the intracellular end of the acid-sensing ion channel pore. / Lynagh, Timothy; Flood, Emelie; Boiteux, Céline; Wulf, Matthias; Komnatnyy, Vitaly V; Colding, Janne M; Allen, Toby W; Pless, Stephan A.

In: eLife, Vol. 6, 24630, 12.05.2017.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Lynagh, T, Flood, E, Boiteux, C, Wulf, M, Komnatnyy, VV, Colding, JM, Allen, TW & Pless, SA 2017, 'A selectivity filter at the intracellular end of the acid-sensing ion channel pore', eLife, vol. 6, 24630. https://doi.org/10.7554/eLife.24630

APA

Lynagh, T., Flood, E., Boiteux, C., Wulf, M., Komnatnyy, V. V., Colding, J. M., Allen, T. W., & Pless, S. A. (2017). A selectivity filter at the intracellular end of the acid-sensing ion channel pore. eLife, 6, [24630]. https://doi.org/10.7554/eLife.24630

Vancouver

Lynagh T, Flood E, Boiteux C, Wulf M, Komnatnyy VV, Colding JM et al. A selectivity filter at the intracellular end of the acid-sensing ion channel pore. eLife. 2017 May 12;6. 24630. https://doi.org/10.7554/eLife.24630

Author

Lynagh, Timothy ; Flood, Emelie ; Boiteux, Céline ; Wulf, Matthias ; Komnatnyy, Vitaly V ; Colding, Janne M ; Allen, Toby W ; Pless, Stephan A. / A selectivity filter at the intracellular end of the acid-sensing ion channel pore. In: eLife. 2017 ; Vol. 6.

Bibtex

@article{35627d9dfeb84f89ace1d195e9eb8904,
title = "A selectivity filter at the intracellular end of the acid-sensing ion channel pore",
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.",
keywords = "Journal Article",
author = "Timothy Lynagh and Emelie Flood and C{\'e}line Boiteux and Matthias Wulf and Komnatnyy, {Vitaly V} and Colding, {Janne M} and Allen, {Toby W} and Pless, {Stephan A}",
year = "2017",
month = may,
day = "12",
doi = "10.7554/eLife.24630",
language = "English",
volume = "6",
journal = "eLife",
issn = "2050-084X",
publisher = "eLife Sciences Publications Ltd.",

}

RIS

TY - JOUR

T1 - A selectivity filter at the intracellular end of the acid-sensing ion channel pore

AU - Lynagh, Timothy

AU - Flood, Emelie

AU - Boiteux, Céline

AU - Wulf, Matthias

AU - Komnatnyy, Vitaly V

AU - Colding, Janne M

AU - Allen, Toby W

AU - Pless, Stephan A

PY - 2017/5/12

Y1 - 2017/5/12

N2 - 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.

AB - 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.

KW - Journal Article

U2 - 10.7554/eLife.24630

DO - 10.7554/eLife.24630

M3 - Journal article

C2 - 28498103

VL - 6

JO - eLife

JF - eLife

SN - 2050-084X

M1 - 24630

ER -

ID: 184802939