ArticleProceedings of the National Academy of Sciences of the United States of America2009
Conformational heterogeneity of the M2 proton channel and a structural model for channel activation.
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 77 papers.
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Who cites it
77 citing papers in PubMed.
- 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
- Conformation and Membrane Topology of the N-Terminal Ectodomain of Influenza A M2 Protein.Membranes · 2025Article
- A combination of solid-state NMR and MD simulations reveals the binding mode of a rhomboid protease inhibitor.Chemical science · 2021Article
- Effects of Cholesterol on the Partitioning of a Drug Molecule in Lipid Bilayers.The journal of physical chemistry. B · 2021Article
- Influenza Viruses: Harnessing the Crucial Role of the M2 Ion-Channel and Neuraminidase toward Inhibitor Design.Molecules (Basel, Switzerland) · 2021Review
- 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
- 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
- The distal cytoplasmic tail of the influenza A M2 protein dynamically extends from the membrane.Biochimica et biophysica acta. Biomembranes · 2019Article
- X-ray Crystal Structure of the Influenza A M2 Proton Channel S31N Mutant in Two Conformational States: An Open and Shut Case.Journal of the American Chemical Society · 2019Article
- Viroporins in the Influenza Virus.Cells · 2019Review
- Hidden motions and motion-induced invisibility: Dynamics-based spectral editing in solid-state NMR.Methods (San Diego, Calif.) · 2018Review
- All-atom virus simulations.Current opinion in virology · 2018Review
- Influenza A Virus M2 Protein: Roles from Ingress to Egress.International journal of molecular sciences · 2017Review
- A Budding-Defective M2 Mutant Exhibits Reduced Membrane Interaction, Insensitivity to Cholesterol, and Perturbed Interdomain Coupling.Biochemistry · 2017Article
- Activation pH and Gating Dynamics of Influenza A M2 Proton Channel Revealed by Single-Molecule Spectroscopy.Angewandte Chemie (International ed. in English) · 2017Article
- Binding and Proton Blockage by Amantadine Variants of the Influenza M2Journal of medicinal chemistry · 2017Article
- Affinity of Rimantadine Enantiomers against Influenza A/M2 Protein Revisited.ACS medicinal chemistry letters · 2017Article
- Acid activation mechanism of the influenza A M2 proton channel.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
17 more citing papers are in PubMed but not listed here.
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3 authors.
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Abstract
The M2 protein of influenza virus A is a proton-selective ion channel activated by pH. Structure determination by solid-state and solution NMR and X-ray crystallography has contributed significantly to our understanding, but channel activation may involve conformations not captured by these studies. Indeed, solid-state NMR data demonstrate that the M2 protein possesses significant conformational heterogeneity. Here, we report molecular dynamics (MD) simulations of the M2 transmembrane domain (TMD) in the absence and presence of the antiviral drug amantadine. The ensembles of MD conformations for both apo and bound forms reproduced the NMR data well. The TMD helix was found to kink around Gly-34, where water molecules penetrated deeply into the backbone. The amantadine-bound form exhibited a single peak approximately 10 degrees in the distribution of helix-kink angle, but the apo form exhibited 2 peaks, approximately 0 degrees and 40 degrees . Conformations of the apo form with small and large kink angles had narrow and wide pores, respectively, around the primary gate formed by His-37 and Trp-41. We propose a structural model for channel activation, in which the small-kink conformations dominate before proton uptake by His-37 from the exterior, and proton uptake makes the large-kink conformations more favorable, thereby priming His-37 for proton release to the interior.
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