1. Structural Biology and Molecular Biophysics

Slowly folding surface extension in the prototypic avian hepatitis B virus capsid governs stability

  1. Cihan Makbul
  2. Michael Nassal  Is a corresponding author
  3. Bettina Böttcher  Is a corresponding author
  1. Universitat Würzburg, Germany
  2. University Hospital Freiburg, Germany
https://doi.org/10.7554/eLife.57277
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  1. Cihan Makbul
  2. Michael Nassal
  3. Bettina Böttcher
(2020)
Slowly folding surface extension in the prototypic avian hepatitis B virus capsid governs stability
eLife 9:e57277.
https://doi.org/10.7554/eLife.57277
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Abstract

Hepatitis B virus (HBV) is an important but difficult to study human pathogen. Most basics of the hepadnaviral life-cycle were unraveled using duck HBV (DHBV) as a model although DHBV has a capsid protein (CP) comprising ~260 rather than ~180 amino acids. Here we present high-resolution structures of several DHBV capsid-like particles (CLPs) determined by electron cryo-microscopy. As for HBV, DHBV CLPs consist of a dimeric a-helical frame-work with protruding spikes at the dimer interface. A fundamental new feature is a ~45 amino acid proline-rich extension in each monomer replacing the tip of the spikes in HBV CP. In vitro, folding of the extension takes months, implying a catalyzed process in vivo. DHBc variants lacking a folding-proficient extension produced regular CLPs in bacteria but failed to form stable nucleocapsids in hepatoma cells. We propose that the extension domain acts as a conformational switch with differential response options during viral infection.

Data availability

EM-maps are deposited in the EMDB. Where applicable models were deposited in the pdbDHBc capsid: 10800 (EMDB) 6ygh (pdb)DHBC co expressed with FkpA: 10801 (EMDB)DHBC R124E (mutant): 10802 (EMDB)DHBCR124E_del (deletion-mutant): 10803 (EMDB 6ygi (pdb)

The following data sets were generated
The following previously published data sets were used

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Author details

  1. Cihan Makbul

    Lehrstuhl für Biochemie, Universitat Würzburg, Würzburg, Germany
    Competing interests
    The authors declare that no competing interests exist.

  2. Michael Nassal

    Internal Medicine 2/ Molecular Biology, University Hospital Freiburg, Freiburg, Germany
    For correspondence
    nassal2@ukl.uni-freiburg.de
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2204-9158

  3. Bettina Böttcher

    Lehrstuhl für Biochemie, Universitat Würzburg, Würzburg, Germany
    For correspondence
    bettina.boettcher@uni-wuerzburg.de
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7962-4849

Funding

Deutsche Forschungsgemeinschaft (BO1150/17-1)

  • Bettina Böttcher

Deutsche Forschungsgemeinschaft (INST 92/903-1FUGG)

  • Bettina Böttcher

Deutsche Forschungsgemeinschaft (Na154/9-4)

  • Michael Nassal

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

© 2020, Makbul et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Cihan Makbul
  2. Michael Nassal
  3. Bettina Böttcher
(2020)
Slowly folding surface extension in the prototypic avian hepatitis B virus capsid governs stability
eLife 9:e57277.
https://doi.org/10.7554/eLife.57277

Share this article

https://doi.org/10.7554/eLife.57277

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