• Login
    View Item 
    •   Home
    • UA Faculty Research
    • UA Faculty Publications
    • View Item
    •   Home
    • UA Faculty Research
    • UA Faculty Publications
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of UA Campus RepositoryCommunitiesTitleAuthorsIssue DateSubmit DateSubjectsPublisherJournalThis CollectionTitleAuthorsIssue DateSubmit DateSubjectsPublisherJournal

    My Account

    LoginRegister

    About

    AboutUA Faculty PublicationsUA DissertationsUA Master's ThesesUA Honors ThesesUA PressUA YearbooksUA CatalogsUA Libraries

    Statistics

    Most Popular ItemsStatistics by CountryMost Popular Authors

    Protonation equilibria and pore-opening structure of the dual-histidine influenza B virus M2 transmembrane proton channel from solid-state NMR

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Thumbnail
    Name:
    J.Biol.Chem.-2017-Williams-178 ...
    Size:
    2.165Mb
    Format:
    PDF
    Description:
    FInal Published Version
    Download
    Author
    Williams, Jonathan K.
    Shcherbakov, Alexander A.
    Wang, Jun
    Hong, Mei cc
    Affiliation
    Univ Arizona, Dept Pharmacol & Toxicol
    Issue Date
    2017-10-27
    
    Metadata
    Show full item record
    Publisher
    AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
    Citation
    Protonation equilibria and pore-opening structure of the dual-histidine influenza B virus M2 transmembrane proton channel from solid-state NMR 2017, 292 (43):17876 Journal of Biological Chemistry
    Journal
    Journal of Biological Chemistry
    Rights
    © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.
    Collection Information
    This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.
    Abstract
    The influenza A and B viruses are the primary cause of seasonal flu epidemics. Common to both viruses is the M2 protein, a homotetrameric transmembrane proton channel that acidifies the virion after endocytosis. Although influenza A M2 (AM2) and B M2 (BM2) are functional analogs, they have little sequence homology, except for a conserved HXXXW motif, which is responsible for proton selectivity and channel gating. Importantly, BM2contains a second titratable histidine, His-27, in the tetrameric transmembrane domain that forms a reverse WXXXH motif with the gating tryptophan. To understand how His-27 affects the proton conduction property of BM2, we have used solid-state NMR to characterize the pH-dependent structure and dynamics of His-27. In cholesterol-containing lipid membranes mimicking the virus envelope, N-15 NMR spectra show that the His-27 tetrad protonates with higher pKa values than His-19, indicating that the solvent-accessible His-27 facilitates proton conduction of the channel by increasing the proton dissociation rates of His-19. AM2is inhibited by the amantadine class of antiviral drugs, whereas BM2 has no known inhibitors. Wemeasured the N-terminal interhelical separation of the BM2 channel using fluorinated Phe-5. The interhelical F-19-F-19 distances show a bimodal distribution of a short distance of 7 angstrom and a long distance of 15-20 angstrom, indicating that the phenylene rings do not block small-molecule entry into the channel pore. These results give insights into the lack of amantadine inhibition of BM2 and reveal structural diversities in this family of viral proton channels.
    Note
    12 month embargo; Published: 11 Sept 2017
    ISSN
    0021-9258
    1083-351X
    PubMed ID
    28893910
    DOI
    10.1074/jbc.M117.813998
    Version
    Final published version
    Sponsors
    National Institutes of Health [GM088204]
    Additional Links
    http://www.jbc.org/lookup/doi/10.1074/jbc.M117.813998
    ae974a485f413a2113503eed53cd6c53
    10.1074/jbc.M117.813998
    Scopus Count
    Collections
    UA Faculty Publications

    entitlement

    Related articles

    • Solid-State NMR Investigation of the Conformation, Proton Conduction, and Hydration of the Influenza B Virus M2 Transmembrane Proton Channel.
    • Authors: Williams JK, Tietze D, Lee M, Wang J, Hong M
    • Issue date: 2016 Jul 6
    • 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.
    • Authors: Pankratova Y, McKay MJ, Ma C, Tan H, Wang J, Hong M
    • Issue date: 2024 Jul 31
    • Elucidating Relayed Proton Transfer through a His-Trp-His Triad of a Transmembrane Proton Channel by Solid-State NMR.
    • Authors: Kwon B, Roos M, Mandala VS, Shcherbakov AA, Hong M
    • Issue date: 2019 Jun 28
    • Functional studies reveal the similarities and differences between AM2 and BM2 proton channels from influenza viruses.
    • Authors: Ma C, Wang J
    • Issue date: 2018 Feb
    • A unique activation-promotion mechanism of the influenza B M2 proton channel uncovered by multiscale simulations.
    • Authors: Zhang Y, Zhang H, Zheng Q
    • Issue date: 2019 Feb 6
    The University of Arizona Libraries | 1510 E. University Blvd. | Tucson, AZ 85721-0055
    Tel 520-621-6442 | repository@u.library.arizona.edu
    DSpace software copyright © 2002-2017  DuraSpace
    Quick Guide | Contact Us | Send Feedback
    Open Repository is a service operated by 
    Atmire NV
     

    Export search results

    The export option will allow you to export the current search results of the entered query to a file. Different formats are available for download. To export the items, click on the button corresponding with the preferred download format.

    By default, clicking on the export buttons will result in a download of the allowed maximum amount of items.

    To select a subset of the search results, click "Selective Export" button and make a selection of the items you want to export. The amount of items that can be exported at once is similarly restricted as the full export.

    After making a selection, click one of the export format buttons. The amount of items that will be exported is indicated in the bubble next to export format.