ArticleProceedings of the National Academy of Sciences of the United States of America2016
Acid activation mechanism of the influenza A M2 proton channel.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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Who cites it
61 citing papers in PubMed, 110 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
- Hydration-Controlled Proton Transport in Respiratory Complex I.Journal of the American Chemical Society · 2026Article
- Synergistic Interplay of Stimulatory Cofactors in the Activation of Adenylyl Cyclase Isoform 1.The journal of physical chemistry. B · 2025Article
- Structural Transition from Closed to Open for the Influenza A M2 Proton Channel as Observed by Proton-Detected Solid-State NMR.Journal of the American Chemical Society · 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
- Solid-state NMR of membrane peptides and proteins in the lipid cubic phase.Biophysical journal · 2025Article
- Influenza A virus RNA localisation and the interceding trafficking pathways of the host cell.PLoS pathogens · 2025Review
- The Role of Cholesterol in M2 Clustering and Viral Budding Explained.Journal of chemical theory and computation · 2025Article
- The interplay of polarizable water and protein in the activation of the M2 channel.Frontiers in pharmacology · 2025Article
- Activation of the Influenza B M2 Proton Channel (BM2).Biochemistry · 2024Article
- 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
- Innovative Self-Assembly of 15-Mer Chimeric α-Peptide-Oligourea Foldamers toward ClSmall science · 2024Article
- 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
- Activation of the influenza B M2 proton channel (BM2).bioRxiv : the preprint server for biology · 2024Article
- Comparing Multifunctional Viral and Eukaryotic Proteins for Generating Scission Necks in Membranes.ACS nano · 2024Article
- Molecular Dynamics Simulation of Complex Reactivity with the Rapid Approach for Proton Transport and Other Reactions (RAPTOR) Software Package.The journal of physical chemistry. B · 2024Article
- Review
- Transcendent Aspects of Proton Channels.Annual review of physiology · 2024Review
- The M2 proteins of bat influenza A viruses reveal atypical features compared to conventional M2 proteins.Journal of virology · 2023Article
1 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
The homotetrameric influenza A M2 channel (AM2) is an acid-activated proton channel responsible for the acidification of the influenza virus interior, an important step in the viral lifecycle. Four histidine residues (His37) in the center of the channel act as a pH sensor and proton selectivity filter. Despite intense study, the pH-dependent activation mechanism of the AM2 channel has to date not been completely understood at a molecular level. Herein we have used multiscale computer simulations to characterize (with explicit proton transport free energy profiles and their associated calculated conductances) the activation mechanism of AM2. All proton transfer steps involved in proton diffusion through the channel, including the protonation/deprotonation of His37, are explicitly considered using classical, quantum, and reactive molecular dynamics methods. The asymmetry of the proton transport free energy profile under high-pH conditions qualitatively explains the rectification behavior of AM2 (i.e., why the inward proton flux is allowed when the pH is low in viral exterior and high in viral interior, but outward proton flux is prohibited when the pH gradient is reversed). Also, in agreement with electrophysiological results, our simulations indicate that the C-terminal amphipathic helix does not significantly change the proton conduction mechanism in the AM2 transmembrane domain; the four transmembrane helices flanking the channel lumen alone seem to determine the proton conduction mechanism.
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