Evidence map›Paper›PMID 39259593›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2024

Quantitative insights into the mechanism of proton conduction and selectivity for the human voltage-gated proton channel Hv1.

Yu Liu, Chenghan Li, J Alfredo Freites, Douglas J Tobias, Gregory A Voth

Abstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

2 citing papers in PubMed.

  1. Hydration-Controlled Proton Transport in Respiratory Complex I.Journal of the American Chemical Society · 2026
    Article
  2. Fluctuating hydrogen-bond network of the Hv1 ion channel.Computational and structural biotechnology journal · 2025
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors.

Yu LiuDepartment of Chemistry, Chicago Center for Theoretical Chemistry, Institute for Biophysical Dynamics, and James Frank Institute, University of Chicago, Chicago, IL 60637.ORCID 0000-0001-6579-5041
Chenghan LiDepartment of Chemistry, Chicago Center for Theoretical Chemistry, Institute for Biophysical Dynamics, and James Frank Institute, University of Chicago, Chicago, IL 60637.
J Alfredo FreitesDepartment of Chemistry, University of California, Irvine, CA 92697.ORCID 0000-0001-5842-7443
Douglas J TobiasDepartment of Chemistry, University of California, Irvine, CA 92697.
Gregory A VothDepartment of Chemistry, Chicago Center for Theoretical Chemistry, Institute for Biophysical Dynamics, and James Frank Institute, University of Chicago, Chicago, IL 60637.ORCID 0000-0002-3267-6748

Funding

SIMULATIONS OF PROTON TRANSLOCATION IN BIOMOLECULESR01GM053148 · NIGMS · UNIVERSITY OF UTAH · PI VOTH, GREGORY A. · 1996 to 2021
$5.3M
Mechanisms of Permeation and Gating of Voltage-Sensing DomainsR01GM098973 · NIGMS · UNIVERSITY OF CALIFORNIA-IRVINE · PI TOMBOLA, FRANCESCO · 2011 to 2025
$4.5M
HHS | NIH | National Institute of General Medical Sciences (NIGMS) R01GM053148HHS | NIH | National Institute of General Medical Sciences (NIGMS) R01GM098973NIGMS NIH HHS R01 GM053148NIGMS NIH HHS R01 GM098973NSF (NSF) OCI-1053575
6 · The paper itself

Abstract

Human voltage-gated proton (hHv1) channels are crucial for regulating essential biological processes such as immune cell respiratory burst, sperm capacitation, and cancer cell migration. Despite the significant concentration difference between protons and other ions in physiological conditions, hHv1 demonstrates remarkable proton selectivity. Our calculations of single-proton, cation, and anion permeation free energy profiles quantitatively demonstrate that the proton selectivity of the wild-type channel originates from its strong proton affinity via the titration of the key residues D112 and D174, although the channel imposes similar kinetic blocking effects for protons compared to other ions. A two-proton knock-on model is proposed to mathematically explain the electrophysiological measurements of the pH-dependent proton conductance in the conductive state. Moreover, it is shown that the anion selectivity of the D112N mutant channel is tied to impaired proton transport and substantial anion leakage.

Indexed as

Ion ChannelsProtonsHumansHydrogen-Ion ConcentrationIon Channel GatingMutationHVCN1 protein, humanIon ChannelsProtonsion selectivitymolecular dynamicsproton channelproton transport

Identifiers

PMID39259593
PMCPMC11420211

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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 Socratic graph.