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.
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.
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Who cites it
52 citing papers in PubMed, 82 citations in OpenAlex.
- Article
- Interrogating the structure and function of the human voltage-gated proton channel (hHbioRxiv : the preprint server for biology · 2025Article
- Expression and Purification of the Human Voltage-Gated Proton Channel (hHBio-protocol · 2025Article
- A novel method for expressing and purifying large quantities of functional and stable human voltage-gated proton channel (hHProtein science : a publication of the Protein Society · 2025Article
- Biophysical Properties of Somatic Cancer Mutations in the S4 Transmembrane Segment of the Human Voltage-Gated Proton Channel hHBiomolecules · 2025Article
- Fluctuating hydrogen-bond network of the Hv1 ion channel.Computational and structural biotechnology journal · 2025Article
- Dimerization is required for the glycosylation of S1-S2 linker of sea urchin voltage-gated proton channel Hv1.Biophysical journal · 2024Article
- Interior pH-sensing residue of human voltage-gated proton channel HBiophysical journal · 2024Article
- 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 · 2024Article
- Hydrophobic residues in S1 modulate enzymatic function and voltage sensing in voltage-sensing phosphatase.The Journal of general physiology · 2024Article
- The Pentameric Ligand-Gated Ion Channel Family: A New Member of the Voltage Gated Ion Channel Superfamily?International journal of molecular sciences · 2024Article
- Anionic omega currents from single countercharge mutants in the voltage-sensing domain of Ci-VSP.The Journal of general physiology · 2024Article
- Mechanically-primed voltage-gated proton channels from angiosperm plants.Nature communications · 2023Article
- Voltage-Gated Proton Channels in the Tree of Life.Biomolecules · 2023Review
- 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 · 2023Article
- Article
- The role of Phe150 in human voltage-gated proton channel.iScience · 2022Article
- Cholesterol inhibits human voltage-gated proton channel hHv1.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- 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 · 2022Article
- Structural dynamics determine voltage and pH gating in human voltage-gated proton channel.eLife · 2022Article
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8 authors at 3 institutions in 1 country.
Funding
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.
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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.