An aqueous H + permeation pathway in the voltage-gated proton channel Hv1

I. Scott Ramsey, Younes Mokrab, Ingrid Carvacho, Zara A. Sands, Mark S.P. Sansom, David E. Clapham

Research output: Contribution to journalArticle

102 Citations (Scopus)

Abstract

Hv1 voltage-gated proton channels mediate rapid and selective transmembrane H+ flux and are gated by both voltage and pH gradients. Selective H+ transfer in membrane proteins is commonly achieved by Grotthuss proton 'hopping' in chains of ionizable amino acid side chains and intraprotein water molecules. To identify whether ionizable residues are required for proton permeation in Hv1, we neutralized candidate residues and measured expressed voltage-gated H+ currents. Unexpectedly, charge neutralization was insufficient to abrogate either the Hv1 conductance or coupling of pH gradient and voltage-dependent activation. Molecular dynamics simulations revealed water molecules in the central crevice of Hv1 model structures but not in homologous voltage-sensor domain (VSD) structures. Our results indicate that Hv1 most likely forms an internal water wire for selective proton transfer and that interactions between water molecules and S4 arginines may underlie coupling between voltage-and pH-gradient sensing.

Original languageEnglish
Pages (from-to)869-875
Number of pages7
JournalNature Structural and Molecular Biology
Volume17
Issue number7
DOIs
Publication statusPublished - Jul 2010
Externally publishedYes

Fingerprint

Proton-Motive Force
Protons
Water
Molecular Dynamics Simulation
Arginine
Membrane Proteins
Amino Acids

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

Cite this

Ramsey, I. S., Mokrab, Y., Carvacho, I., Sands, Z. A., Sansom, M. S. P., & Clapham, D. E. (2010). An aqueous H + permeation pathway in the voltage-gated proton channel Hv1. Nature Structural and Molecular Biology, 17(7), 869-875. https://doi.org/10.1038/nsmb.1826

An aqueous H + permeation pathway in the voltage-gated proton channel Hv1. / Ramsey, I. Scott; Mokrab, Younes; Carvacho, Ingrid; Sands, Zara A.; Sansom, Mark S.P.; Clapham, David E.

In: Nature Structural and Molecular Biology, Vol. 17, No. 7, 07.2010, p. 869-875.

Research output: Contribution to journalArticle

Ramsey, I. Scott ; Mokrab, Younes ; Carvacho, Ingrid ; Sands, Zara A. ; Sansom, Mark S.P. ; Clapham, David E. / An aqueous H + permeation pathway in the voltage-gated proton channel Hv1. In: Nature Structural and Molecular Biology. 2010 ; Vol. 17, No. 7. pp. 869-875.
@article{281f32dc01ed46daa9731589032a6092,
title = "An aqueous H + permeation pathway in the voltage-gated proton channel Hv1",
abstract = "Hv1 voltage-gated proton channels mediate rapid and selective transmembrane H+ flux and are gated by both voltage and pH gradients. Selective H+ transfer in membrane proteins is commonly achieved by Grotthuss proton 'hopping' in chains of ionizable amino acid side chains and intraprotein water molecules. To identify whether ionizable residues are required for proton permeation in Hv1, we neutralized candidate residues and measured expressed voltage-gated H+ currents. Unexpectedly, charge neutralization was insufficient to abrogate either the Hv1 conductance or coupling of pH gradient and voltage-dependent activation. Molecular dynamics simulations revealed water molecules in the central crevice of Hv1 model structures but not in homologous voltage-sensor domain (VSD) structures. Our results indicate that Hv1 most likely forms an internal water wire for selective proton transfer and that interactions between water molecules and S4 arginines may underlie coupling between voltage-and pH-gradient sensing.",
author = "Ramsey, {I. Scott} and Younes Mokrab and Ingrid Carvacho and Sands, {Zara A.} and Sansom, {Mark S.P.} and Clapham, {David E.}",
year = "2010",
month = "7",
doi = "10.1038/nsmb.1826",
language = "English",
volume = "17",
pages = "869--875",
journal = "Nature Structural and Molecular Biology",
issn = "1545-9993",
publisher = "Nature Publishing Group",
number = "7",

}

TY - JOUR

T1 - An aqueous H + permeation pathway in the voltage-gated proton channel Hv1

AU - Ramsey, I. Scott

AU - Mokrab, Younes

AU - Carvacho, Ingrid

AU - Sands, Zara A.

AU - Sansom, Mark S.P.

AU - Clapham, David E.

PY - 2010/7

Y1 - 2010/7

N2 - Hv1 voltage-gated proton channels mediate rapid and selective transmembrane H+ flux and are gated by both voltage and pH gradients. Selective H+ transfer in membrane proteins is commonly achieved by Grotthuss proton 'hopping' in chains of ionizable amino acid side chains and intraprotein water molecules. To identify whether ionizable residues are required for proton permeation in Hv1, we neutralized candidate residues and measured expressed voltage-gated H+ currents. Unexpectedly, charge neutralization was insufficient to abrogate either the Hv1 conductance or coupling of pH gradient and voltage-dependent activation. Molecular dynamics simulations revealed water molecules in the central crevice of Hv1 model structures but not in homologous voltage-sensor domain (VSD) structures. Our results indicate that Hv1 most likely forms an internal water wire for selective proton transfer and that interactions between water molecules and S4 arginines may underlie coupling between voltage-and pH-gradient sensing.

AB - Hv1 voltage-gated proton channels mediate rapid and selective transmembrane H+ flux and are gated by both voltage and pH gradients. Selective H+ transfer in membrane proteins is commonly achieved by Grotthuss proton 'hopping' in chains of ionizable amino acid side chains and intraprotein water molecules. To identify whether ionizable residues are required for proton permeation in Hv1, we neutralized candidate residues and measured expressed voltage-gated H+ currents. Unexpectedly, charge neutralization was insufficient to abrogate either the Hv1 conductance or coupling of pH gradient and voltage-dependent activation. Molecular dynamics simulations revealed water molecules in the central crevice of Hv1 model structures but not in homologous voltage-sensor domain (VSD) structures. Our results indicate that Hv1 most likely forms an internal water wire for selective proton transfer and that interactions between water molecules and S4 arginines may underlie coupling between voltage-and pH-gradient sensing.

UR - http://www.scopus.com/inward/record.url?scp=77954383905&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77954383905&partnerID=8YFLogxK

U2 - 10.1038/nsmb.1826

DO - 10.1038/nsmb.1826

M3 - Article

C2 - 20543828

AN - SCOPUS:77954383905

VL - 17

SP - 869

EP - 875

JO - Nature Structural and Molecular Biology

JF - Nature Structural and Molecular Biology

SN - 1545-9993

IS - 7

ER -