ArticleJournal of molecular biology2009
Structure of amantadine-bound M2 transmembrane peptide of influenza A in lipid bilayers from magic-angle-spinning solid-state NMR: the role of Ser31 in amantadine binding.
Article in Journal of molecular biology, 2009. 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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93 citing papers in PubMed, 146 citations in OpenAlex.
- Anle138b binds predominantly to the central cavity in lipidic Aβ₄₀ fibrils and modulates fibril formation.Nature communications · 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 protocols for unveiling dynamics and (drug) interactions of membrane-bound proteins.Protein science : a publication of the Protein Society · 2025Article
- Solid-State NMR of Virus Membrane Proteins.Accounts of chemical research · 2025Article
- Transmembrane conformation of the envelope protein of an alpha coronavirus, NL63.Protein science : a publication of the Protein Society · 2024Article
- New type of RNA virus replication inhibitor based on decahydro-closo-decaborate anion containing amino acid ester pendant group.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2022Article
- Clustering of tetrameric influenza M2 peptides in lipid bilayers investigated byBiochimica et biophysica acta. Biomembranes · 2022Article
- Virus Structures and Dynamics by Magic-Angle Spinning NMR.Annual review of virology · 2021Review
- Trends and strategies to combat viral infections: A review on FDA approved antiviral drugs.International journal of biological macromolecules · 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
- Review
- Protein NMR Spectroscopy at 150 kHz Magic-Angle Spinning Continues To Improve Resolution and Mass Sensitivity.Chembiochem : a European journal of chemical biology · 2020Article
- Put a cork in it: Plugging the M2 viral ion channel to sink influenza.Antiviral research · 2020Review
- Imidazole-Imidazole Hydrogen Bonding in the pH-Sensing Histidine Side Chains of Influenza A M2.Journal of the American Chemical Society · 2020Article
- Observation of the Imidazole-Imidazolium Hydrogen Bonds Responsible for Selective Proton Conductance in the Influenza A M2 Channel.Journal of the American Chemical Society · 2020Article
- Modulation of Transmembrane Domain Interactions in Neu Receptor Tyrosine Kinase by Membrane Fluidity and Cholesterol.The Journal of membrane biology · 2019Article
- Interplay between membrane curvature and protein conformational equilibrium investigated by solid-state NMR.Journal of structural biology · 2019Article
- Inhibitors of the M2 Proton Channel Engage and Disrupt Transmembrane Networks of Hydrogen-Bonded Waters.Journal of the American Chemical Society · 2018Article
- Unraveling the Binding, Proton Blockage, and Inhibition of Influenza M2 WT and S31N by Rimantadine Variants.ACS medicinal chemistry letters · 2018Article
- Review
33 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The M2 proton channel of influenza A is the target of the antiviral drugs amantadine and rimantadine, whose effectiveness has been abolished by a single-site mutation of Ser31 to Asn in the transmembrane domain of the protein. Recent high-resolution structures of the M2 transmembrane domain obtained from detergent-solubilized protein in solution and crystal environments gave conflicting drug binding sites. We present magic-angle-spinning solid-state NMR results of Ser31 and a number of other residues in the M2 transmembrane peptide (M2TMP) bound to lipid bilayers. Comparison of the spectra of the membrane-bound apo and complexed M2TMP indicates that Ser31 is the site of the largest chemical shift perturbation by amantadine. The chemical shift constraints lead to a monomer structure with a small kink of the helical axis at Gly34. A tetramer model is then constructed using the helix tilt angle and several interhelical distances previously measured on unoriented bilayer samples. This tetramer model differs from the solution and crystal structures in terms of the openness of the N-terminus of the channel, the constriction at Ser31, and the side-chain conformations of Trp41, a residue important for channel gating. Moreover, the tetramer model suggests that Ser31 may interact with amantadine amine via hydrogen bonding. While the apo and drug-bound M2TMP have similar average structures, the complexed peptide has much narrower linewidths at physiological temperature, indicating drug-induced changes of the protein dynamics in the membrane. Further, at low temperature, several residues show narrower lines in the complexed peptide than the apo peptide, indicating that amantadine binding reduces the conformational heterogeneity of specific residues. The differences of the current solid-state NMR structure of the bilayer-bound M2TMP from the detergent-based M2 structures suggest that the M2 conformation is sensitive to the environment, and care must be taken when interpreting structural findings from non-bilayer samples.
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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.