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

ELife
Timothy LynaghStephan A Pless

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.

References

Aug 1, 1975·Chemistry and Physics of Lipids·N O PetersenS I Chan
Jun 1, 1972·The Journal of General Physiology·B Hille
Feb 1, 1996·Journal of Molecular Graphics·W HumphreyK Schulten
Mar 13, 1997·Nature·R WaldmannM Lazdunski
Mar 1, 1985·Physical Review A: General Physics·W G Hoover
Nov 25, 1985·Physical Review Letters·R Car, M Parrinello
Mar 31, 1999·Proceedings of the National Academy of Sciences of the United States of America·S KellenbergerL Schild
Jul 10, 1999·The Journal of General Physiology·S KellenbergerL Schild
Sep 25, 1999·The Journal of Biological Chemistry·P M SnyderD B Bucher
Nov 11, 1999·Pflügers Archiv : European journal of physiology·S GründerB C Rossier
Feb 9, 2000·American Journal of Physiology. Cell Physiology·A L LanglohD J Benos
Mar 18, 2000·The Journal of Biological Chemistry·S ShengT R Kleyman
Sep 21, 2001·The Journal of Biological Chemistry·S ShengT R Kleyman
Nov 2, 2001·Nature·S Bernèche, B Roux
Nov 28, 2001·The Journal of General Physiology·S KellenbergerL Schild
Jun 28, 2002·Physiological Reviews·Stephan Kellenberger, Laurent Schild
Mar 23, 2004·Nucleic Acids Research·Robert C Edgar
Jun 26, 2004·Proceedings of the National Academy of Sciences of the United States of America·David S DahanHenry A Lester
Oct 14, 2005·Journal of Computational Chemistry·James C PhillipsKlaus Schulten
Feb 25, 2006·The Journal of Biological Chemistry·Yvan PfisterLaurent Schild
Sep 21, 2007·Nature·Jayasankar JastiEric Gouaux
Feb 19, 2008·Journal of Molecular Biology·Sergei Y Noskov, Benoît Roux
May 16, 2009·Journal of Computational Chemistry·B R BrooksM Karplus
May 26, 2010·The Journal of Physical Chemistry. B·Jeffery B KlaudaRichard W Pastor
Sep 23, 2010·Langmuir : the ACS Journal of Surfaces and Colloids·Eugenia Iskrenova-TchoukovaR James Kirkpatrick
Jul 12, 2011·Nature·Jian PayandehWilliam A Catterall
Jul 21, 2011·Nature Communications·Tianbo LiCecilia M Canessa
Jul 26, 2011·Nature Chemical Biology·Stephan A PlessChristopher A Ahern
Mar 1, 2012·The Journal of Biological Chemistry·Marcelo D Carattino, Margaret C Della Vecchia
Sep 26, 2012·The Journal of General Physiology·Stefan DürrnagelStefan Gründer
Aug 9, 2013·The Journal of Physical Chemistry. B·Richard M VenableRichard W Pastor

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Citations

Mar 8, 2018·Nature·Nate YoderEric Gouaux
Aug 4, 2018·Chembiochem : a European Journal of Chemical Biology·Vita SereikaitėKristian Strømgaard
Oct 14, 2017·Molecular Pharmacology·Axel SchmidtStefan Gründer
Jan 18, 2020·The Journal of General Physiology·Timothy LynaghStephan A Pless
Apr 20, 2020·The Journal of Physiology·Matthew L RookDavid M MacLean
Jul 28, 2020·The Journal of Physiology·N BraunS A Pless
Aug 24, 2018·The Journal of General Physiology·Lei Yang, Lawrence G Palmer
Feb 6, 2020·The Journal of General Physiology·Robert C KlippJohn R Bankston
Aug 1, 2018·Proceedings of the National Academy of Sciences of the United States of America·Timothy LynaghStephan A Pless
Oct 22, 2019·Biophysical Journal·Marina A KasimovaStephan Alexander Pless
Jun 28, 2019·Chemical Reviews·Emelie FloodToby W Allen
Aug 27, 2021·The Journal of General Physiology·Zeshan P SheikhStephan A Pless
Jan 6, 2021·Journal of the American Chemical Society·Christian R O BartlingKristian Strømgaard
Nov 13, 2021·The Journal of General Physiology·Zhuyuan ChenCecilia M Canessa

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Methods Mentioned

BETA
X-ray
PCR

Software Mentioned

Clampfit
CHARMM27
4NTW
VMD
Prism
ParseFEP
2QTS
CHARMM
GraphPad
NAMD

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