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

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

Article and author information

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.

Reviewing Editor

  1. Wenhui Li, National Institute of Biological Sciences, China

Publication history

  1. Received: March 26, 2020
  2. Accepted: August 13, 2020
  3. Accepted Manuscript published: August 14, 2020 (version 1)
  4. Version of Record published: August 28, 2020 (version 2)

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