Evidence map›Paper›PMID 26443860›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2015

Resting state of the human proton channel dimer in a lipid bilayer.

Qufei Li, Rong Shen, Jeremy S Treger, Sherry S Wanderling, Wieslawa Milewski, Klaudia Siwowska, Francisco Bezanilla, Eduardo Perozo

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.

0numbers the graph read from it
0cells of the map it votes in
52citing papers in PubMed
4.7field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

52 citing papers in PubMed, 82 citations in OpenAlex.

  1. Article
  2. Article
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  5. Article
  6. Fluctuating hydrogen-bond network of the Hv1 ion channel.Computational and structural biotechnology journal · 2025
    Article
  7. Article
  8. Article
  9. Quantitative insights into the mechanism of proton conduction and selectivity for the human voltage-gated proton channel Hv1.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  10. Article
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  13. Article
  14. Review
  15. Structural basis for severe pain caused by mutations in the S4-S5 linkers of voltage-gated sodium channel NaProceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  16. Article
  17. Article
  18. Cholesterol inhibits human voltage-gated proton channel hHv1.Proceedings of the National Academy of Sciences of the United States of America · 2022
    Article
  19. Molecular determinants of inhibition of the human proton channel hHv1 by the designer peptide C6 and a bivalent derivative.Proceedings of the National Academy of Sciences of the United States of America · 2022
    Article
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 3 institutions in 1 country.

Qufei LiDepartment of Biochemistry and Molecular Biology, The University of Chicago, Chicago, IL 60637 eperozo@uchicago.edu fqli@uchicago.edu.
Rong ShenDepartment of Biochemistry and Molecular Biology, The University of Chicago, Chicago, IL 60637.
Jeremy S TregerDepartment of Biochemistry and Molecular Biology, The University of Chicago, Chicago, IL 60637.
Sherry S WanderlingDepartment of Biochemistry and Molecular Biology, The University of Chicago, Chicago, IL 60637.
Wieslawa MilewskiDepartment of Biochemistry and Molecular Biology, The University of Chicago, Chicago, IL 60637.
Klaudia SiwowskaDepartment of Biochemistry and Molecular Biology, The University of Chicago, Chicago, IL 60637.
Francisco BezanillaDepartment of Biochemistry and Molecular Biology, The University of Chicago, Chicago, IL 60637.
Eduardo PerozoDepartment of Biochemistry and Molecular Biology, The University of Chicago, Chicago, IL 60637 eperozo@uchicago.edu fqli@uchicago.edu.
Boston Children's Hospital · USHoward Hughes Medical Institute · USUniversity of Chicago · US

Funding

MEDICAL SCIENTIST TRAININGT32GM007281 · NIGMS · UNIVERSITY OF CHICAGO · PI CLARK, MARCUS RAMSAY · 1985 to 2022
$32.1M
Subproject 5U54GM074946 · NIGMS · UNIVERSITY OF CALIF-LOS ALAMOS NAT LAB · PI TERWILLIGER, THOMAS C. · 2005 to 2009
$20.2M
TrainingP41GM103712 · NIGMS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI FAEDER, JAMES · 2012 to 2021
$16.3M
HIGH RESOLUTION STRUCTURAL DYNAMICS OF K CHANNELSR01GM057846 · NIGMS · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI PEROZO, EDUARDO A · 1998 to 2018
$7.4M
Beagle-2S10OD018495 · OD · UNIVERSITY OF CHICAGO · PI FOSTER, IAN · 2014 to 2014
$2.0M
NIGMS NIH HHS P41 GM103712NIGMS NIH HHS P41GM103712-S1NIGMS NIH HHS R01 GM057846NIGMS NIH HHS R01-GM57846NIGMS NIH HHS T32 GM007281NIGMS NIH HHS U54 GM074946NIGMS NIH HHS U54 GM74946NIH HHS 1S10OD018495-01NIH HHS S10 OD018495
6 · The paper itself

Abstract

The voltage-gated proton channel Hv1 plays a critical role in the fast proton translocation that underlies a wide range of physiological functions, including the phagocytic respiratory burst, sperm motility, apoptosis, and metastatic cancer. Both voltage activation and proton conduction are carried out by a voltage-sensing domain (VSD) with strong similarity to canonical VSDs in voltage-dependent cation channels and enzymes. We set out to determine the structural properties of membrane-reconstituted human proton channel (hHv1) in its resting conformation using electron paramagnetic resonance spectroscopy together with biochemical and computational methods. We evaluated existing structural templates and generated a spectroscopically constrained model of the hHv1 dimer based on the Ci-VSD structure at resting state. Mapped accessibility data revealed deep water penetration through hHv1, suggesting a highly focused electric field, comprising two turns of helix along the fourth transmembrane segment. This region likely contains the H(+) selectivity filter and the conduction pore. Our 3D model offers plausible explanations for existing electrophysiological and biochemical data, offering an explicit mechanism for voltage activation based on a one-click sliding helix conformational rearrangement.

Indexed as

Lipid BilayersProtonsAmino Acid SequenceDimerizationHumansIon Channel GatingIon ChannelsMolecular Sequence DataIon ChannelsLipid BilayersProtonsEPRMD simulationproton channelvoltage sensing domain

Identifiers

PMID26443860
PMCPMC4640771
OpenAlexW2200595658

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.