Slowly folding surface extension in the prototypic avian hepatitis B virus capsid governs stability
- Universitat Würzburg, Germany
- 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)
Article and author information
Author details
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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Slowly folding surface extension in the prototypic avian hepatitis B virus capsid governs stability
eLife 9:e57277.
https://doi.org/10.7554/eLife.57277
