XB-ART-53677

Elife.
March 3, 2017;
6
## A selectivity filter at the intracellular end of the acid-sensing ion channel pore.

Lynagh T
,
Flood E
,
Boiteux C
,
Wulf M
,
Komnatnyy VV
,
Colding JM
,
Allen TW
,
Pless SA
.

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.

PubMed ID: 28498103

PMC ID: PMC5449180

Article link: Elife.

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Boiteux, 2014, Pubmed

Brooks, 2009, Pubmed

Car, 1999, Pubmed

Carattino, 2012, Pubmed, Xenbase

Cashin, 2007, Pubmed, Xenbase

Dahan, 2004, Pubmed, Xenbase

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Dougherty, 2014, Pubmed, Xenbase

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Gründer, 2015, Pubmed

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Hong, 1994, Pubmed, Xenbase

Hoover, 1999, Pubmed

Humphrey, 1996, Pubmed

Iskrenova-Tchoukova, 2010, Pubmed

Jasti, 2007, Pubmed

Jing, 2013, Pubmed

Kellenberger, 2002, Pubmed

Kellenberger, 2001, Pubmed, Xenbase

Kellenberger, 1999, Pubmed, Xenbase

Kellenberger, 1999, Pubmed, Xenbase

Klauda, 2010, Pubmed

Kreple, 2014, Pubmed

Langloh, 2000, Pubmed, Xenbase

Li, 2011, Pubmed, Xenbase

Li, 2011, Pubmed, Xenbase

Lu, 2001, Pubmed, Xenbase

MacKerell, 2014, Pubmed

Mackerell, 2004, Pubmed

Mansoor, 2016, Pubmed

Marinelli, 2014, Pubmed

Noskov, 2008, Pubmed

Noskov, 2004, Pubmed

Nowak, 1998, Pubmed, Xenbase

Payandeh, 2011, Pubmed

Petersen, 1975, Pubmed

Pfister, 2006, Pubmed, Xenbase

Phillips, 2005, Pubmed

Pidoplichko, 2014, Pubmed

Pless, 2011, Pubmed, Xenbase

Roux, 2010, Pubmed

Sheng, 2000, Pubmed, Xenbase

Sheng, 2001, Pubmed, Xenbase

Snyder, 1999, Pubmed

Venable, 2013, Pubmed

Voilley, 2001, Pubmed

Waldmann, 1997, Pubmed, Xenbase

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Wemmie, 2002, Pubmed

Wu, 2016, Pubmed

Xiong, 2004, Pubmed

Yang, 2014, Pubmed, Xenbase

Yang, 2009, Pubmed

Ziemann, 2009, Pubmed [-]

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