ReviewProtein science : a publication of the Protein Society2012
Structural basis for proton conduction and inhibition by the influenza M2 protein.
Review in Protein science : a publication of the Protein Society, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 papers.
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Who cites it
93 citing papers in PubMed, 139 citations in OpenAlex.
- Roles of the M2 protein of influenza A virus.Virus genes · 2026Review
- Adamantane-based inhibitors of the influenza A M2 proton channel: structure-based design, biological evaluation, and synthetic approaches.RSC medicinal chemistry · 2026Review
- Conserved Transmembrane Asparagine Is Essential for the Ion-Conducting Structure and Dynamics of the SARS-CoV-2 Envelope Protein.Journal of the American Chemical Society · 2026Article
- Side Chain Structures of the Proton-Selective Histidine and Gating Tryptophan in Influenza BM2 Reveal Both Conservation and Variation of the Proton Conduction Mechanism.Biochemistry · 2025Article
- Advances in Viroporin Function and Structure: A Comparative Analysis of Alphavirus 6K with Well-Characterized Viroporins.Viruses · 2025Review
- Solid-State NMR of Virus Membrane Proteins.Accounts of chemical research · 2025Article
- Activation of the Influenza B M2 Proton Channel (BM2).Biochemistry · 2024Article
- Oligomeric State and Drug Binding of the SARS-CoV-2 Envelope Protein Are Sensitive to the Ectodomain.Journal of the American Chemical Society · 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
- Hexamethylene amiloride binds the SARS-CoV-2 envelope protein at the protein-lipid interface.Protein science : a publication of the Protein Society · 2023Article
- Rapid Determination of the Topology of Oligomeric α-Helical Membrane Proteins by Water- and Lipid-Edited Methyl NMR.The journal of physical chemistry. B · 2023Article
- The M2 proteins of bat influenza A viruses reveal atypical features compared to conventional M2 proteins.Journal of virology · 2023Article
- Molecular origins of asymmetric proton conduction in the influenza M2 channel.Biophysical journal · 2023Article
- Clustering of tetrameric influenza M2 peptides in lipid bilayers investigated byBiochimica et biophysica acta. Biomembranes · 2022Article
- From Angstroms to Nanometers: Measuring Interatomic Distances by Solid-State NMR.Chemical reviews · 2022Review
- pH- and Calcium-Dependent Aromatic Network in the SARS-CoV-2 Envelope Protein.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
- Rational design of a deuterium-containing M2-S31N channel blocker UAWJ280 withEmerging microbes & infections · 2021Article
33 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
The influenza M2 protein forms an acid-activated and drug-sensitive proton channel in the virus envelope that is important for the virus lifecycle. The functional properties and high-resolution structures of this proton channel have been extensively studied to understand the mechanisms of proton conduction and drug inhibition. We review biochemical and electrophysiological studies of M2 and discuss how high-resolution structures have transformed our understanding of this proton channel. Comparison of structures obtained in different membrane-mimetic solvents and under different pH using X-ray crystallography, solution NMR, and solid-state NMR spectroscopy revealed how the M2 structure depends on the environment and showed that the pharmacologically relevant drug-binding site lies in the transmembrane (TM) pore. Competing models of proton conduction have been evaluated using biochemical experiments, high-resolution structural methods, and computational modeling. These results are converging to a model in which a histidine residue in the TM domain mediates proton relay with water, aided by microsecond conformational dynamics of the imidazole ring. These mechanistic insights are guiding the design of new inhibitors that target drug-resistant M2 variants and may be relevant for other proton channels.
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Registered trials
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.