ArticleJournal of molecular biology2015
Mapping the gating and permeation pathways in the voltage-gated proton channel Hv1.
Article in Journal of molecular biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 34 citations in OpenAlex.
- Modulators of the Human Voltage-Gated Proton Channel HPharmaceuticals (Basel, Switzerland) · 2025Review
- Identification of a Novel Structural Class of HJournal of chemical information and modeling · 2024Article
- Transcendent Aspects of Proton Channels.Annual review of physiology · 2024Review
- Review
- Voltage-Gated Proton Channels in the Tree of Life.Biomolecules · 2023Review
- Article
- Voltage-gated proton channels in polyneopteran insects.FEBS open bio · 2022Article
- HIFs: New arginine mimic inhibitors of the Hv1 channel with improved VSD-ligand interactions.The Journal of general physiology · 2021Article
- The voltage sensor is responsible for ΔpH dependence in HProceedings of the National Academy of Sciences of the United States of America · 2021Article
- Structural Mechanism of ω-Currents in a Mutated Kv7.2 Voltage Sensor Domain from Molecular Dynamics Simulations.Journal of chemical information and modeling · 2021Article
- Functions and Mechanisms of the Voltage-Gated Proton Channel Hv1 in Brain and Spinal Cord Injury.Frontiers in cellular neuroscience · 2021Review
- Engineered high-affinity zinc binding site reveals gating configurations of a human proton channel.The Journal of general physiology · 2020Article
- Roles for Countercharge in the Voltage Sensor Domain of Ion Channels.Frontiers in pharmacology · 2020Review
- Hydrophobic gasket mutation produces gating pore currents in closed human voltage-gated proton channels.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- On the control of the proton current in the voltage-gated proton channel Hv1.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Voltage and pH sensing by the voltage-gated proton channel, HJournal of the Royal Society, Interface · 2018Review
- CrossTalk opposing view: proton transfer in Hv1 utilizes a water wire, and does not require transient protonation of a conserved aspartate in the S1 transmembrane helix.The Journal of physiology · 2017Article
- Does Proton Conduction in the Voltage-Gated HThe journal of physical chemistry. B · 2017Article
- On the role of water density fluctuations in the inhibition of a proton channel.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- The Hv1 proton channel responds to mechanical stimuli.The Journal of general physiology · 2016Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Voltage-gated proton channels (Hv1) are ubiquitous throughout nature and are implicated in numerous physiological processes. The gene encoding for Hv1, however, was only identified in 2006. The lack of sufficient structural information of this channel has hampered the understanding of the molecular mechanism of channel activation and proton permeation. This study uses both simulation and experimental approaches to further develop existing models of the Hv1 channel. Our study provides insights into features of channel gating and proton permeation pathway. We compare open- and closed-state structures developed previously with a recent crystal structure that traps the channel in a presumably closed state. Insights into gating pathways were provided using a combination of all-atom molecular dynamics simulations with a swarm of trajectories with the string method for extensive transition path sampling and evolution. A detailed residue-residue interaction profile and a hydration profile were studied to map the gating pathway in this channel. In particular, it allows us to identify potential intermediate states and compare them to the experimentally observed crystal structure of Takeshita et al. (Takeshita K, Sakata S, Yamashita E, Fujiwara Y, Kawanabe A, Kurokawa T, et al. X-ray crystal structure of voltage-gated proton channel. Nature 2014). The mechanisms governing ion transport in the wild-type and mutant Hv1 channels were studied by a combination of electrophysiological recordings and free energy simulations. With these results, we were able to further refine ideas about the location and function of the selectivity filter. The refined structural models will be essential for future investigations of this channel and the development of new drugs targeting cellular proton transport.
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Registered trials
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.