ArticleThe Journal of physiology2010
Zinc inhibition of monomeric and dimeric proton channels suggests cooperative gating.
Article in The Journal of physiology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.
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Who cites it
74 citing papers in PubMed, 104 citations in OpenAlex.
- Article
- Modulators of the Human Voltage-Gated Proton Channel HPharmaceuticals (Basel, Switzerland) · 2025Review
- Brain targeted lipid nanoparticles with Hv1 inhibitors alleviate neuroinflammation post-ischemic stroke.Journal of nanobiotechnology · 2025Article
- The Role of Ion-Transporting Proteins on Crosstalk Between the Skeletal Muscle and Central Nervous Systems Elicited by Physical Exercise.Molecular neurobiology · 2025Review
- Biophysical Properties of Somatic Cancer Mutations in the S4 Transmembrane Segment of the Human Voltage-Gated Proton Channel hHBiomolecules · 2025Article
- Interior pH-sensing residue of human voltage-gated proton channel HBiophysical journal · 2024Article
- Interaction with stomatin directs human proton channels into cholesterol-dependent membrane domains.Biophysical journal · 2024Article
- Temperature Dependent Activity of the Voltage-Gated Proton Channel.Advances in experimental medicine and biology · 2024Review
- Voltage-Gated Proton Channels in the Tree of Life.Biomolecules · 2023Review
- Microglial reprogramming by Hv1 antagonism protects neurons from inflammatory and glutamate toxicity.Journal of neurochemistry · 2023Article
- Unexpected expansion of the voltage-gated proton channel family.The FEBS journal · 2023Article
- 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
- Voltage-gated proton channels in polyneopteran insects.FEBS open bio · 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
- Zinc modulation of proton currents in a new voltage-gated proton channel suggests a mechanism of inhibition.The FEBS journal · 2020Article
- Engineered high-affinity zinc binding site reveals gating configurations of a human proton channel.The Journal of general physiology · 2020Article
- The voltage-gated proton channel hHv1 is functionally expressed in human chorion-derived mesenchymal stem cells.Scientific reports · 2020Article
- Assessing Structural Determinants of ZnBiophysical journal · 2020Article
14 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Voltage-gated proton channels are strongly inhibited by Zn(2+), which binds to His residues. However, in a molecular model, the two externally accessible His are too far apart to coordinate Zn(2+). We hypothesize that high-affinity Zn(2+) binding occurs at the dimer interface between pairs of His residues from both monomers. Consistent with this idea, Zn(2+) effects were weaker in monomeric channels. Mutation of His(193) and His(140) in various combinations and in tandem dimers revealed that channel opening was slowed by Zn(2+) only when at least one His was present in each monomer, suggesting that in wild-type (WT) H(V)1, Zn(2+) binding between His of both monomers inhibits channel opening. In addition, monomeric channels opened exponentially, and dimeric channels opened sigmoidally. Monomeric channel gating had weaker temperature dependence than dimeric channels. Finally, monomeric channels opened 6.6 times faster than dimeric channels. Together, these observations suggest that in the proton channel dimer, the two monomers are closely apposed and interact during a cooperative gating process. Zn(2+) appears to slow opening by preventing movement of the monomers relative to each other that is prerequisite to opening. These data also suggest that the association of the monomers is tenuous and allows substantial freedom of movement. The data support the idea that native proton channels are dimeric. Finally, the idea that monomer-dimer interconversion occurs during activation of phagocytes appears to be ruled out.
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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.