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TitleSlowly folding surface extension in the prototypic avian hepatitis B virus capsid governs stability.
Journal, issue, pagesElife, Vol. 9, Year 2020
Publish dateAug 14, 2020
AuthorsCihan Makbul / Michael Nassal / Bettina Böttcher /
PubMed AbstractHepatitis 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 ...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 α-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.
External linksElife / PubMed:32795390 / PubMed Central
MethodsEM (single particle)
Resolution3.0 - 6.2 Å
Structure data

10800

6ygh

EMDB-10800, PDB-6ygh:
Duck hepatitis B virus capsid
Method: EM (single particle) / Resolution: 3.7 Å

EMDB-10801:
Folding of extension domain in duck hepatitis B virus capsids is accelerated by FkpA
Method: EM (single particle) / Resolution: 3.9 Å

EMDB-10802:
The Mutant Duck Hepatitis B core protein R124E has a disordered extension domain
Method: EM (single particle) / Resolution: 6.2 Å

10803

6ygi

EMDB-10803, PDB-6ygi:
Duck hepatitis B virus capsid Mutant R124E_delta78-122
Method: EM (single particle) / Resolution: 3.0 Å

Source
  • hepatitis b virus duck/dhbv-16
KeywordsVIRUS LIKE PARTICLE / duck hepatitis B core protein / extension domain / spike / slowly folding

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