High-resolution structure of the open NaK channel

Amer Alam, Youxing Jiang

Research output: Contribution to journalArticle

92 Citations (Scopus)

Abstract

We report the crystal structure of the nonselective cation channel NaK from Bacillus cereus at a resolution of 1.6 Å. The structure reveals the intracellular gate in an open state, as opposed to the closed form reported previously, making NaK the only channel for which the three-dimensional structures of both conformations are known. Channel opening follows a conserved mechanism of inner helix bending using a flexible glycine residue, the gating hinge, seen in MthK and most other tetrameric cation channels. Additionally, distinct inter and intrasubunit rearrangements involved in channel gating are seen and characterized for the first time along with inner helix twisting motions. Furthermore, we identify a residue deeper within the cavity of the channel pore, Phe92, which is likely to form a constriction point within the open pore, restricting ion flux through the channel. Mutating this residue to alanine causes a subsequent increase in ion-conduction rates as measured by 86Rb flux assays. The structures of both the open and closed conformations of the NaK channel correlate well with those of equivalent K + channel conformations, namely MthK and KcsA, respectively.

Original languageEnglish (US)
Pages (from-to)30-34
Number of pages5
JournalNature Structural and Molecular Biology
Volume16
Issue number1
DOIs
StatePublished - Jan 2009

Fingerprint

Cations
Ions
Constriction
Alanine
Glycine
prokaryotic potassium channel

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

Cite this

High-resolution structure of the open NaK channel. / Alam, Amer; Jiang, Youxing.

In: Nature Structural and Molecular Biology, Vol. 16, No. 1, 01.2009, p. 30-34.

Research output: Contribution to journalArticle

@article{52053454562a4c5e8d97d7456d5272e4,
title = "High-resolution structure of the open NaK channel",
abstract = "We report the crystal structure of the nonselective cation channel NaK from Bacillus cereus at a resolution of 1.6 {\AA}. The structure reveals the intracellular gate in an open state, as opposed to the closed form reported previously, making NaK the only channel for which the three-dimensional structures of both conformations are known. Channel opening follows a conserved mechanism of inner helix bending using a flexible glycine residue, the gating hinge, seen in MthK and most other tetrameric cation channels. Additionally, distinct inter and intrasubunit rearrangements involved in channel gating are seen and characterized for the first time along with inner helix twisting motions. Furthermore, we identify a residue deeper within the cavity of the channel pore, Phe92, which is likely to form a constriction point within the open pore, restricting ion flux through the channel. Mutating this residue to alanine causes a subsequent increase in ion-conduction rates as measured by 86Rb flux assays. The structures of both the open and closed conformations of the NaK channel correlate well with those of equivalent K + channel conformations, namely MthK and KcsA, respectively.",
author = "Amer Alam and Youxing Jiang",
year = "2009",
month = "1",
doi = "10.1038/nsmb.1531",
language = "English (US)",
volume = "16",
pages = "30--34",
journal = "Nature Structural and Molecular Biology",
issn = "1545-9993",
publisher = "Nature Publishing Group",
number = "1",

}

TY - JOUR

T1 - High-resolution structure of the open NaK channel

AU - Alam, Amer

AU - Jiang, Youxing

PY - 2009/1

Y1 - 2009/1

N2 - We report the crystal structure of the nonselective cation channel NaK from Bacillus cereus at a resolution of 1.6 Å. The structure reveals the intracellular gate in an open state, as opposed to the closed form reported previously, making NaK the only channel for which the three-dimensional structures of both conformations are known. Channel opening follows a conserved mechanism of inner helix bending using a flexible glycine residue, the gating hinge, seen in MthK and most other tetrameric cation channels. Additionally, distinct inter and intrasubunit rearrangements involved in channel gating are seen and characterized for the first time along with inner helix twisting motions. Furthermore, we identify a residue deeper within the cavity of the channel pore, Phe92, which is likely to form a constriction point within the open pore, restricting ion flux through the channel. Mutating this residue to alanine causes a subsequent increase in ion-conduction rates as measured by 86Rb flux assays. The structures of both the open and closed conformations of the NaK channel correlate well with those of equivalent K + channel conformations, namely MthK and KcsA, respectively.

AB - We report the crystal structure of the nonselective cation channel NaK from Bacillus cereus at a resolution of 1.6 Å. The structure reveals the intracellular gate in an open state, as opposed to the closed form reported previously, making NaK the only channel for which the three-dimensional structures of both conformations are known. Channel opening follows a conserved mechanism of inner helix bending using a flexible glycine residue, the gating hinge, seen in MthK and most other tetrameric cation channels. Additionally, distinct inter and intrasubunit rearrangements involved in channel gating are seen and characterized for the first time along with inner helix twisting motions. Furthermore, we identify a residue deeper within the cavity of the channel pore, Phe92, which is likely to form a constriction point within the open pore, restricting ion flux through the channel. Mutating this residue to alanine causes a subsequent increase in ion-conduction rates as measured by 86Rb flux assays. The structures of both the open and closed conformations of the NaK channel correlate well with those of equivalent K + channel conformations, namely MthK and KcsA, respectively.

UR - http://www.scopus.com/inward/record.url?scp=58149250085&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=58149250085&partnerID=8YFLogxK

U2 - 10.1038/nsmb.1531

DO - 10.1038/nsmb.1531

M3 - Article

VL - 16

SP - 30

EP - 34

JO - Nature Structural and Molecular Biology

JF - Nature Structural and Molecular Biology

SN - 1545-9993

IS - 1

ER -