ArticleProceedings of the National Academy of Sciences of the United States of America2010
Proton and cation transport activity of the M2 proton channel from influenza A virus.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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Who cites it
60 citing papers in PubMed, 91 citations in OpenAlex.
- Roles of the M2 protein of influenza A virus.Virus genes · 2026Review
- Active pH Modulation by Proton Channel-Peptide Nucleic Acid Complex for Effective siRNA Endosomal Escape.Small (Weinheim an der Bergstrasse, Germany) · 2026Article
- Comparative Genomics of Viral Genomes and Identification of Three Novel Viroporin-Like Superfamilies.Microbial physiology · 2026Article
- 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
- Conformation and Membrane Topology of the N-Terminal Ectodomain of Influenza A M2 Protein.Membranes · 2025Article
- The M2 proteins of bat influenza A viruses reveal atypical features compared to conventional M2 proteins.Journal of virology · 2023Article
- A structure and knowledge-based combinatorial approach to engineering universal scFv antibodies against influenza M2 protein.Journal of biomedical science · 2023Article
- Transient water wires mediate selective proton transport in designed channel proteins.Nature chemistry · 2023Article
- Antiviral Approaches against Influenza Virus.Clinical microbiology reviews · 2023Review
- Biomimetic Artificial Proton Channels.Biomolecules · 2022Review
- Enhancing neutralizing activity against influenza H1N1/PR8 by engineering a single-domain VL-M2 specific into a bivalent form.PloS one · 2022Article
- 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
- The Structure, Function, and Pathobiology of the Influenza A and B Virus Ion Channels.Cold Spring Harbor perspectives in medicine · 2020Review
- Site-directed M2 proton channel inhibitors enable synergistic combination therapy for rimantadine-resistant pandemic influenza.PLoS pathogens · 2020Article
- Put a cork in it: Plugging the M2 viral ion channel to sink influenza.Antiviral research · 2020Review
- M2 amphipathic helices facilitate pH-dependent conformational transition in influenza A virus.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- M2e-based universal influenza vaccines: a historical overview and new approaches to development.Journal of biomedical science · 2019Review
- The distal cytoplasmic tail of the influenza A M2 protein dynamically extends from the membrane.Biochimica et biophysica acta. Biomembranes · 2019Article
- Proton-Induced Conformational and Hydration Dynamics in the Influenza A M2 Channel.Journal of the American Chemical Society · 2019Article
- Model of influenza virus acidification.PloS one · 2019Article
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
The M2 protein is a small, single-span transmembrane (TM) protein from the influenza A virus. This virus enters cells via endosomes; as the endosomes mature and become more acidic M2 facilitates proton transport into the viral interior, thereby disrupting matrix protein/RNA interactions required for infectivity. A mystery has been how protons can accumulate in the viral interior without developing a large electrical potential that impedes further inward proton translocation. Progress in addressing this question has been limited by the availability of robust methods of unidirectional insertion of the protein into virus-like vesicles. Using an optimized procedure for reconstitution, we show that M2 has antiporter-like activity, facilitating K(+) or Na(+) efflux when protons flow down a concentration gradient into the vesicles. Cation efflux is very small except under conditions mimicking those encountered by the endosomally entrapped virus, in which protons are flowing through the channel. This proton/cation exchange function is consistent with the known high proton selectivity of the channel. Thus, M2 acts as a proton uniporter that occasionally allows K(+) to flow to maintain electrical neutrality. Remarkably, as the pH inside M2-containing vesicles (pH(in)) decreases, the proton channel activity of M2 is inhibited, but its cation transport activity is activated. This reciprocal inhibition of proton flux and activation of cation flux with decreasing pH(in) first allows accumulation of protons in the early stages of acidification, then trapping of protons within the virus when low pH(in) is achieved.
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