ArticleProceedings of the National Academy of Sciences of the United States of America2014
Hydrophobic plug functions as a gate in voltage-gated proton channels.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 86 citations in OpenAlex.
- Mutagenesis-Centered Integrative Approaches for Identifying Binding Sites in Ion Channels and Uncovering Modulatory Mechanisms.Advances in experimental medicine and biology · 2026Review
- 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
- Transcendent Aspects of Proton Channels.Annual review of physiology · 2024Review
- Review
- Trapping Charge Mechanism in Hv1 Channels (International journal of molecular sciences · 2023Article
- Mechanically-primed voltage-gated proton channels from angiosperm plants.Nature communications · 2023Article
- Transient water wires mediate selective proton transport in designed channel proteins.Nature chemistry · 2023Article
- Voltage-Gated Proton Channels in the Tree of Life.Biomolecules · 2023Review
- The role of Phe150 in human voltage-gated proton channel.iScience · 2022Article
- A Review on the Role of Bicarbonate and Proton Transporters during Sperm Capacitation in Mammals.International journal of molecular sciences · 2022Review
- Gating Mechanism of the Voltage-Gated Proton Channel Studied by Molecular Dynamics Simulations.Molecules (Basel, Switzerland) · 2022Article
- Analysis of an electrostatic mechanism for ΔpH dependent gating of the voltage-gated proton channel, HBiochimica et biophysica acta. Bioenergetics · 2021Review
- A novel Hv1 inhibitor reveals a new mechanism of inhibition of a voltage-sensing domain.The Journal of general physiology · 2021Article
- HIFs: New arginine mimic inhibitors of the Hv1 channel with improved VSD-ligand interactions.The Journal of general physiology · 2021Article
- Hydropathicity-based prediction of pain-causing NaV1.7 variants.BMC bioinformatics · 2021Article
- Mathematical Modeling of Ion Quantum Tunneling Reveals Novel Properties of Voltage-Gated Channels and Quantum Aspects of Their Pathophysiology in Excitability-Related Disorders.Pathophysiology : the official journal of the International Society for Pathophysiology · 2021Article
- Voltage-gated proton channels from fungi highlight role of peripheral regions in channel activation.Communications biology · 2021Article
- Refinement of a cryo-EM structure of hERG: Bridging structure and function.Biophysical journal · 2021Article
- Molecular Simulations of Hydrophobic Gating of Pentameric Ligand Gated Ion Channels: Insights into Water and Ions.The journal of physical chemistry. B · 2021Article
- Engineered high-affinity zinc binding site reveals gating configurations of a human proton channel.The Journal of general physiology · 2020Article
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Voltage-gated proton (Hv1) channels play important roles in the respiratory burst, in pH regulation, in spermatozoa, in apoptosis, and in cancer metastasis. Unlike other voltage-gated cation channels, the Hv1 channel lacks a centrally located pore formed by the assembly of subunits. Instead, the proton permeation pathway in the Hv1 channel is within the voltage-sensing domain of each subunit. The gating mechanism of this pathway is still unclear. Mutagenic and fluorescence studies suggest that the fourth transmembrane (TM) segment (S4) functions as a voltage sensor and that there is an outward movement of S4 during channel activation. Using thermodynamic mutant cycle analysis, we find that the conserved positively charged residues in S4 are stabilized by countercharges in the other TM segments both in the closed and open states. We constructed models of both the closed and open states of Hv1 channels that are consistent with the mutant cycle analysis. These structural models suggest that electrostatic interactions between TM segments in the closed state pull hydrophobic residues together to form a hydrophobic plug in the center of the voltage-sensing domain. Outward S4 movement during channel activation induces conformational changes that remove this hydrophobic plug and instead insert protonatable residues in the center of the channel that, together with water molecules, can form a hydrogen bond chain across the channel for proton permeation. This suggests that salt bridge networks and the hydrophobic plug function as the gate in Hv1 channels and that outward movement of S4 leads to the opening of this gate.
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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.