IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-36219-3.html
   My bibliography  Save this article

Molecular elucidation of drug-induced abnormal assemblies of the hepatitis B virus capsid protein by solid-state NMR

Author

Listed:
  • Lauriane Lecoq

    (UMR 5086 CNRS/Université de Lyon)

  • Louis Brigandat

    (UMR 5086 CNRS/Université de Lyon)

  • Rebecca Huber

    (UMR 5086 CNRS/Université de Lyon)

  • Marie-Laure Fogeron

    (UMR 5086 CNRS/Université de Lyon)

  • Shishan Wang

    (UMR 5086 CNRS/Université de Lyon)

  • Marie Dujardin

    (UMR 5086 CNRS/Université de Lyon)

  • Mathilde Briday

    (UMR 5086 CNRS/Université de Lyon)

  • Thomas Wiegand

    (ETH Zurich
    Max-Planck-Institute for Chemical Energy Conversion
    RWTH Aachen University)

  • Morgane Callon

    (ETH Zurich)

  • Alexander Malär

    (ETH Zurich)

  • David Durantel

    (UMR 5286, Centre Léon Bérard)

  • Dara Burdette

    (Gilead Sciences)

  • Jan Martin Berke

    (Janssen Pharmaceutica N.V)

  • Beat H. Meier

    (ETH Zurich)

  • Michael Nassal

    (University of Freiburg)

  • Anja Böckmann

    (UMR 5086 CNRS/Université de Lyon)

Abstract

Hepatitis B virus (HBV) capsid assembly modulators (CAMs) represent a recent class of anti-HBV antivirals. CAMs disturb proper nucleocapsid assembly, by inducing formation of either aberrant assemblies (CAM-A) or of apparently normal but genome-less empty capsids (CAM-E). Classical structural approaches have revealed the CAM binding sites on the capsid protein (Cp), but conformational information on the CAM-induced off-path aberrant assemblies is lacking. Here we show that solid-state NMR can provide such information, including for wild-type full-length Cp183, and we find that in these assemblies, the asymmetric unit comprises a single Cp molecule rather than the four quasi-equivalent conformers typical for the icosahedral T = 4 symmetry of the normal HBV capsids. Furthermore, while in contrast to truncated Cp149, full-length Cp183 assemblies appear, on the mesoscopic level, unaffected by CAM-A, NMR reveals that on the molecular level, Cp183 assemblies are equally aberrant. Finally, we use a eukaryotic cell-free system to reveal how CAMs modulate capsid-RNA interactions and capsid phosphorylation. Our results establish a structural view on assembly modulation of the HBV capsid, and they provide a rationale for recently observed differences between in-cell versus in vitro capsid assembly modulation.

Suggested Citation

  • Lauriane Lecoq & Louis Brigandat & Rebecca Huber & Marie-Laure Fogeron & Shishan Wang & Marie Dujardin & Mathilde Briday & Thomas Wiegand & Morgane Callon & Alexander Malär & David Durantel & Dara Bur, 2023. "Molecular elucidation of drug-induced abnormal assemblies of the hepatitis B virus capsid protein by solid-state NMR," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-36219-3
    DOI: 10.1038/s41467-023-36219-3
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-36219-3
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-36219-3?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. B. Böttcher & S. A. Wynne & R. A. Crowther, 1997. "Determination of the fold of the core protein of hepatitis B virus by electron cryomicroscopy," Nature, Nature, vol. 386(6620), pages 88-91, March.
    2. Ian Graber-Stiehl, 2018. "The silent epidemic killing more people than HIV, malaria or TB," Nature, Nature, vol. 564(7734), pages 24-26, December.
    3. Thomas Wiegand & Riccardo Cadalbert & Denis Lacabanne & Joanna Timmins & Laurent Terradot & Anja Böckmann & Beat H. Meier, 2019. "The conformational changes coupling ATP hydrolysis and translocation in a bacterial DnaB helicase," Nature Communications, Nature, vol. 10(1), pages 1-11, December.
    4. Peixiang Ma & Yi Xue & Nicolas Coquelle & Jens D. Haller & Tairan Yuwen & Isabel Ayala & Oleg Mikhailovskii & Dieter Willbold & Jacques-Philippe Colletier & Nikolai R. Skrynnikov & Paul Schanda, 2015. "Observing the overall rocking motion of a protein in a crystal," Nature Communications, Nature, vol. 6(1), pages 1-10, December.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Bhakta, Sayan & van Heel, Marin, 2024. "Single-Particle Cryo-EM: What happens inside the Black Box?," OSF Preprints 5empt, Center for Open Science.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-36219-3. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.