ArticleThe Journal of general physiology2013
Peregrination of the selectivity filter delineates the pore of the human voltage-gated proton channel hHV1.
Article in The Journal of general physiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 42 citations in OpenAlex.
- Transcendent Aspects of Proton Channels.Annual review of physiology · 2024Review
- Voltage-Gated Proton Channels in the Tree of Life.Biomolecules · 2023Review
- Role of voltage-gated proton channel (Hv1) in cancer biology.Frontiers in pharmacology · 2023Review
- Analysis of an electrostatic mechanism for ΔpH dependent gating of the voltage-gated proton channel, HBiochimica et biophysica acta. Bioenergetics · 2021Review
- Zinc modulation of proton currents in a new voltage-gated proton channel suggests a mechanism of inhibition.The FEBS journal · 2020Article
- Zn2+ to probe voltage-gated proton (Hv1) channels.The Journal of general physiology · 2020Article
- Engineered high-affinity zinc binding site reveals gating configurations of a human proton channel.The Journal of general physiology · 2020Article
- Voltage-dependent structural models of the human Hv1 proton channel from long-timescale molecular dynamics simulations.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- 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
- Outlining the proton-conduction pathway in otopetrin channels.Nature structural & molecular biology · 2019Article
- HistidineThe Journal of general physiology · 2018Article
- Voltage and pH sensing by the voltage-gated proton channel, HJournal of the Royal Society, Interface · 2018Review
- Rebuttal from Ashley L. Bennett and Ian Scott Ramsey.The Journal of physiology · 2017Article
- 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
- Rebuttal from Thomas E. DeCoursey.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 intimate and controversial relationship between voltage-gated proton channels and the phagocyte NADPH oxidase.Immunological reviews · 2016Review
- Article
- Insights into the structure and function of HV1 from a meta-analysis of mutation studies.The Journal of general physiology · 2016Review
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Authors and funding
8 authors at 5 institutions in 2 countries.
Funding
Abstract
Extraordinary selectivity is crucial to all proton-conducting molecules, including the human voltage-gated proton channel (hHV1), because the proton concentration is >10(6) times lower than that of other cations. Here we use "selectivity filter scanning" to elucidate the molecular requirements for proton-specific conduction in hHV1. Asp(112), in the middle of the S1 transmembrane helix, is an essential part of the selectivity filter in wild-type (WT) channels. After neutralizing Asp(112) by mutating it to Ala (D112A), we introduced Asp at each position along S1 from 108 to 118, searching for "second site suppressor" activity. Surprisingly, most mutants lacked even the anion conduction exhibited by D112A. Proton-specific conduction was restored only with Asp or Glu at position 116. The D112V/V116D channel strikingly resembled WT in selectivity, kinetics, and ΔpH-dependent gating. The S4 segment of this mutant has similar accessibility to WT in open channels, because R211H/D112V/V116D was inhibited by internally applied Zn(2+). Asp at position 109 allowed anion permeation in combination with D112A but did not rescue function in the nonconducting D112V mutant, indicating that selectivity is established externally to the constriction at F150. The three positions that permitted conduction all line the pore in our homology model, clearly delineating the conduction pathway. Evidently, a carboxyl group must face the pore directly to enable conduction. Molecular dynamics simulations indicate reorganization of hydrogen bond networks in the external vestibule in D112V/V116D. At both positions where it produces proton selectivity, Asp frequently engages in salt linkage with one or more Arg residues from S4. Surprisingly, mean hydration profiles were similar in proton-selective, anion-permeable, and nonconducting constructs. That the selectivity filter functions in a new location helps to define local environmental features required to produce proton-selective conduction.
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