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Structure and mechanism of the M2 proton channel of influenza A virus

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  • Jason R. Schnell

    (Harvard Medical School, Boston, Massachusetts 02115, USA)

  • James J. Chou

    (Harvard Medical School, Boston, Massachusetts 02115, USA)

Abstract

Influenza changes channels Until recently, the pH-gated proton channel of influenza A virus, M2, was effectively targeted by amantadine-based antivirals, but resistance to these drugs is now widespread. Two groups now present structural studies of M2 proton channel. Jason Schnell and James Chou determine the structure of a 38-residue segment of M2, in complex with rimantadine, by NMR spectroscopy. Amanda Stouffer et al. determined the crystal structure of a 25-residue fragment of M2, with and without amantadine, using X-ray diffraction. Strikingly, the resulting structures suggest two very different mechanisms by which the drug inhibits the channel. The proposed mechanisms are discussed by Christopher Miller in an accompanying News & Views article.

Suggested Citation

  • Jason R. Schnell & James J. Chou, 2008. "Structure and mechanism of the M2 proton channel of influenza A virus," Nature, Nature, vol. 451(7178), pages 591-595, January.
    • Handle: RePEc:nat:nature:v:451:y:2008:i:7178:d:10.1038_nature06531
    DOI: 10.1038/nature06531
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    Cited by:

    1. Jianzhao Gao & Wei Cui & Yajun Sheng & Jishou Ruan & Lukasz Kurgan, 2016. "PSIONplus: Accurate Sequence-Based Predictor of Ion Channels and Their Types," PLOS ONE, Public Library of Science, vol. 11(4), pages 1-18, April.
    2. Robert Dobosz & Jan Mućko & Ryszard Gawinecki, 2020. "Using Chou’s 5-Step Rule to Evaluate the Stability of Tautomers: Susceptibility of 2-[(Phenylimino)-methyl]-cyclohexane-1,3-diones to Tautomerization Based on the Calculated Gibbs Free Energies," Energies, MDPI, vol. 13(1), pages 1-14, January.
    3. L. Eyer & K. Hruska, 2013. "Antiviral agents targeting the influenza virus: a review and publication analysis," Veterinární medicína, Czech Academy of Agricultural Sciences, vol. 58(3), pages 113-185.
    4. Bi-Qing Li & Le-Le Hu & Lei Chen & Kai-Yan Feng & Yu-Dong Cai & Kuo-Chen Chou, 2012. "Prediction of Protein Domain with mRMR Feature Selection and Analysis," PLOS ONE, Public Library of Science, vol. 7(6), pages 1-14, June.
    5. Xingya Li & Gengping Jiang & Meipeng Jian & Chen Zhao & Jue Hou & Aaron W. Thornton & Xinyi Zhang & Jefferson Zhe Liu & Benny D. Freeman & Huanting Wang & Lei Jiang & Huacheng Zhang, 2023. "Construction of angstrom-scale ion channels with versatile pore configurations and sizes by metal-organic frameworks," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    6. Mattia L DiFrancesco & Ulf-Peter Hansen & Gerhard Thiel & Anna Moroni & Indra Schroeder, 2014. "Effect of Cytosolic pH on Inward Currents Reveals Structural Characteristics of the Proton Transport Cycle in the Influenza A Protein M2 in Cell-Free Membrane Patches of Xenopus oocytes," PLOS ONE, Public Library of Science, vol. 9(9), pages 1-12, September.
    7. Kuo-Chen Chou & Hong-Bin Shen, 2010. "Plant-mPLoc: A Top-Down Strategy to Augment the Power for Predicting Plant Protein Subcellular Localization," PLOS ONE, Public Library of Science, vol. 5(6), pages 1-11, June.
    8. Zhisong He & Jian Zhang & Xiao-He Shi & Le-Le Hu & Xiangyin Kong & Yu-Dong Cai & Kuo-Chen Chou, 2010. "Predicting Drug-Target Interaction Networks Based on Functional Groups and Biological Features," PLOS ONE, Public Library of Science, vol. 5(3), pages 1-8, March.
    9. Kuo-Chen Chou & Hong-Bin Shen, 2010. "A New Method for Predicting the Subcellular Localization of Eukaryotic Proteins with Both Single and Multiple Sites: Euk-mPLoc 2.0," PLOS ONE, Public Library of Science, vol. 5(4), pages 1-9, April.

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