ArticleProceedings of the National Academy of Sciences of the United States of America2009
Identification of the functional core of the influenza A virus A/M2 proton-selective ion channel.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 113 papers.
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Who cites it
113 citing papers in PubMed, 170 citations in OpenAlex.
- Active pH Modulation by Proton Channel-Peptide Nucleic Acid Complex for Effective siRNA Endosomal Escape.Small (Weinheim an der Bergstrasse, Germany) · 2026Article
- Adamantane-based inhibitors of the influenza A M2 proton channel: structure-based design, biological evaluation, and synthetic approaches.RSC medicinal chemistry · 2026Review
- Engineered Channel Asymmetry Extends Hydrogen-Bonding Networks for Proton Conduction.bioRxiv : the preprint server for biology · 2026Article
- Acquisition of amantadine resistance via M gene reassortment in canine H3N2 influenza virus and elucidation of the resistance mechanism.Virology journal · 2026Article
- CW ESR spectroscopy and protein spin labeling in membrane biology.Physical biology · 2025Review
- Bat Influenza M2 Shows Functions Similar to Those of Classical Influenza A Viruses.Pathogens (Basel, Switzerland) · 2025Article
- Molecular biophysics and inhibition mechanism of influenza virus A M2 viroporin by adamantane-based drugs - Challenges in designing antiviral agents.Journal of structural biology: X · 2025Article
- The Role of Cholesterol in M2 Clustering and Viral Budding Explained.Journal of chemical theory and computation · 2025Article
- Structure and dynamics of the proton-selective histidine and the gating tryptophan in an inward rectifying hybrid influenza B and A virus M2 proton channel.Physical chemistry chemical physics : PCCP · 2024Article
- Real-time tracking of drug binding to influenza A M2 reveals a high energy barrier.Journal of structural biology: X · 2023Article
- Transient water wires mediate selective proton transport in designed channel proteins.Nature chemistry · 2023Article
- Molecular origins of asymmetric proton conduction in the influenza M2 channel.Biophysical journal · 2023Article
- Emulating Membrane Protein Environments─How Much Lipid Is Required for a Native Structure: Influenza S31N M2.Journal of the American Chemical Society · 2022Article
- Multiscale Simulation of an Influenza A M2 Channel Mutant Reveals Key Features of Its Markedly Different Proton Transport Behavior.Journal of the American Chemical Society · 2022Article
- Spiers Memorial Lecture: Analysis andFaraday discussions · 2021Article
- Amantadine has potential for the treatment of COVID-19 because it inhibits known and novel ion channels encoded by SARS-CoV-2.Communications biology · 2021Article
- Acetonitrile allows indirect replacement of nondeuterated lipid detergents by deuterated lipid detergents for the nuclear magnetic resonance study of detergent-soluble proteins.Protein science : a publication of the Protein Society · 2021Article
- Rimantadine Binds to and Inhibits the Influenza A M2 Proton Channel without Enantiomeric Specificity.Biochemistry · 2021Article
- From Acid Activation Mechanisms of Proton Conduction to Design of Inhibitors of the M2 Proton Channel of Influenza A Virus.Frontiers in molecular biosciences · 2021Review
- Influenza A M2 Inhibitor Binding Understood through Mechanisms of Excess Proton Stabilization and Channel Dynamics.Journal of the American Chemical Society · 2020Article
53 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
Abstract
The influenza A virus M2 protein (A/M2) is a homotetrameric pH-activated proton transporter/channel that mediates acidification of the interior of endosomally encapsulated virus. This 97-residue protein has a single transmembrane (TM) helix, which associates to form homotetramers that bind the anti-influenza drug amantadine. However, the minimal fragment required for assembly and proton transport in cellular membranes has not been defined. Therefore, the conductance properties of truncation mutants expressed in Xenopus oocytes were examined. A short fragment spanning residues 21-61, M2(21-61), was inserted into the cytoplasmic membrane and had specific, amantadine-sensitive proton transport activity indistinguishable from that of full-length A/M2; an epitope-tagged version of an even shorter fragment, M2(21-51)-FLAG, had specific activity within a factor of 2 of the full-length protein. Furthermore, synthetic fragments including a peptide spanning residues 22-46 were found to transport protons into liposomes in an amantadine-sensitive manner. In addition, the functionally important His-37 residue pK(a) values are highly perturbed in the tetrameric form of the protein, a property conserved in the TM peptide and full-length A/M2 in both micelles and bilayers. These data demonstrate that the determinants for folding, drug binding, and proton translocation are packaged in a remarkably small peptide that can now be studied with confidence.
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