Gating at the Selectivity Filter of Ion Channels that Conduct Na+ and K+ Ions

Simone Furini; Carmen Domene

doi:10.1016/j.bpj.2011.08.035

Gating at the Selectivity Filter of Ion Channels that Conduct Na+ and K+ Ions

Simone Furini, Carmen Domene^*

^*Corresponding author for this work

Chemistry

University of Siena

Research output: Contribution to journal › Article › peer-review

18 Citations (Scopus)

Abstract

The NaK channel is a cation selective channel with similar permeability for K+ and Na+. The available crystallographic structure of wild-type (WT) NaK is usually associated with a conductive state of the channel. Here, potential of mean force for complete conduction events of Na+ and K+ ions through NaK show that: i), large energy barriers prevent the passage of ions through the WT NaK structure, ii), the barriers are correlated to the presence of a hydrogen bond between Asp-66 and Asn-68, and iii), the structure of NaK mutated to mimic cyclic nucleotide-gated channels conducts Na+ and K+. These results support the hypothesis that the filter of cation selective channels can adopt at least two different structures: a conductive one, represented by the x-ray structures of the NaK-CNG chimeras, and a closed one, represented by the x-ray structures of the WT NaK.

Original language	English
Pages (from-to)	1623-1631
Number of pages	9
Journal	Biophysical Journal
Volume	101
Issue number	7
Early online date	27 Sept 2011
DOIs	https://doi.org/10.1016/j.bpj.2011.08.035
Publication status	Published - 5 Oct 2011

Keywords

TETRAMERIC CATION CHANNELS
X-RAY-STRUCTURE
POTASSIUM-CHANNEL
MOLECULAR-DYNAMICS
CRYSTAL-STRUCTURE
POTENTIAL FUNCTIONS
BINDING-SITES
KCSA
MECHANISM
INACTIVATION

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title = "Gating at the Selectivity Filter of Ion Channels that Conduct Na+ and K+ Ions",

abstract = "The NaK channel is a cation selective channel with similar permeability for K+ and Na+. The available crystallographic structure of wild-type (WT) NaK is usually associated with a conductive state of the channel. Here, potential of mean force for complete conduction events of Na+ and K+ ions through NaK show that: i), large energy barriers prevent the passage of ions through the WT NaK structure, ii), the barriers are correlated to the presence of a hydrogen bond between Asp-66 and Asn-68, and iii), the structure of NaK mutated to mimic cyclic nucleotide-gated channels conducts Na+ and K+. These results support the hypothesis that the filter of cation selective channels can adopt at least two different structures: a conductive one, represented by the x-ray structures of the NaK-CNG chimeras, and a closed one, represented by the x-ray structures of the WT NaK.",

keywords = "TETRAMERIC CATION CHANNELS, X-RAY-STRUCTURE, POTASSIUM-CHANNEL, MOLECULAR-DYNAMICS, CRYSTAL-STRUCTURE, POTENTIAL FUNCTIONS, BINDING-SITES, KCSA, MECHANISM, INACTIVATION",

author = "Simone Furini and Carmen Domene",

year = "2011",

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doi = "10.1016/j.bpj.2011.08.035",

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T1 - Gating at the Selectivity Filter of Ion Channels that Conduct Na+ and K+ Ions

AU - Furini, Simone

AU - Domene, Carmen

PY - 2011/10/5

Y1 - 2011/10/5

N2 - The NaK channel is a cation selective channel with similar permeability for K+ and Na+. The available crystallographic structure of wild-type (WT) NaK is usually associated with a conductive state of the channel. Here, potential of mean force for complete conduction events of Na+ and K+ ions through NaK show that: i), large energy barriers prevent the passage of ions through the WT NaK structure, ii), the barriers are correlated to the presence of a hydrogen bond between Asp-66 and Asn-68, and iii), the structure of NaK mutated to mimic cyclic nucleotide-gated channels conducts Na+ and K+. These results support the hypothesis that the filter of cation selective channels can adopt at least two different structures: a conductive one, represented by the x-ray structures of the NaK-CNG chimeras, and a closed one, represented by the x-ray structures of the WT NaK.

AB - The NaK channel is a cation selective channel with similar permeability for K+ and Na+. The available crystallographic structure of wild-type (WT) NaK is usually associated with a conductive state of the channel. Here, potential of mean force for complete conduction events of Na+ and K+ ions through NaK show that: i), large energy barriers prevent the passage of ions through the WT NaK structure, ii), the barriers are correlated to the presence of a hydrogen bond between Asp-66 and Asn-68, and iii), the structure of NaK mutated to mimic cyclic nucleotide-gated channels conducts Na+ and K+. These results support the hypothesis that the filter of cation selective channels can adopt at least two different structures: a conductive one, represented by the x-ray structures of the NaK-CNG chimeras, and a closed one, represented by the x-ray structures of the WT NaK.

KW - TETRAMERIC CATION CHANNELS

KW - X-RAY-STRUCTURE

KW - POTASSIUM-CHANNEL

KW - MOLECULAR-DYNAMICS

KW - CRYSTAL-STRUCTURE

KW - POTENTIAL FUNCTIONS

KW - BINDING-SITES

KW - KCSA

KW - MECHANISM

KW - INACTIVATION

U2 - 10.1016/j.bpj.2011.08.035

DO - 10.1016/j.bpj.2011.08.035

M3 - Article

SN - 0006-3495

VL - 101

SP - 1623

EP - 1631

JO - Biophysical Journal

JF - Biophysical Journal

IS - 7

ER -

Gating at the Selectivity Filter of Ion Channels that Conduct Na+ and K+ Ions

Abstract

Keywords

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