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-Structure paper
Title | HBV RNA pre-genome encodes specific motifs that mediate interactions with the viral core protein that promote nucleocapsid assembly. |
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Journal, issue, pages | Nat Microbiol, Vol. 2, Page 17098, Year 2017 |
Publish date | Jun 19, 2017 |
![]() | Nikesh Patel / Simon J White / Rebecca F Thompson / Richard Bingham / Eva U Weiß / Daniel P Maskell / Adam Zlotnick / Eric Dykeman / Roman Tuma / Reidun Twarock / Neil A Ranson / Peter G Stockley / ![]() ![]() |
PubMed Abstract | Formation of the hepatitis B virus nucleocapsid is an essential step in the viral lifecycle, but its assembly is not fully understood. We report the discovery of sequence-specific interactions ...Formation of the hepatitis B virus nucleocapsid is an essential step in the viral lifecycle, but its assembly is not fully understood. We report the discovery of sequence-specific interactions between the viral pre-genome and the hepatitis B core protein that play roles in defining the nucleocapsid assembly pathway. Using RNA SELEX and bioinformatics, we identified multiple regions in the pre-genomic RNA with high affinity for core protein dimers. These RNAs form stem-loops with a conserved loop motif that trigger sequence-specific assembly of virus-like particles (VLPs) at much higher fidelity and yield than in the absence of RNA. The RNA oligos do not interact with preformed RNA-free VLPs, so their effects must occur during particle assembly. Asymmetric cryo-electron microscopy reconstruction of the T = 4 VLPs assembled in the presence of one of the RNAs reveals a unique internal feature connected to the main core protein shell via lobes of density. Biophysical assays suggest that this is a complex involving several RNA oligos interacting with the C-terminal arginine-rich domains of core protein. These core protein-RNA contacts may play one or more roles in regulating the organization of the pre-genome during nucleocapsid assembly, facilitating subsequent reverse transcription and acting as a nucleation complex for nucleocapsid assembly. |
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Methods | EM (single particle) |
Resolution | 4.7 - 11.4 Å |
Structure data | ![]() EMDB-3714: ![]() EMDB-3715: ![]() EMDB-3716: |
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