bi500732b_si_001.pdf (112.21 kB)
The Hepatitis B Virus Core Protein Intradimer Interface Modulates Capsid Assembly and Stability
journal contribution
posted on 2015-12-17, 04:02 authored by Lisa Selzer, Sarah
P. Katen, Adam ZlotnickDuring the hepatitis B virus (HBV)
life cycle, capsid assembly
and disassembly must ensure correct packaging and release of the viral
genome. Here we show that changes in the dynamics of the core protein
play an important role in regulating these processes. The HBV capsid
assembles from 120 copies of the core protein homodimer. Each monomer
contains a conserved cysteine at position 61 that can form an intradimer
disulfide that we use as a marker for dimer conformational states.
We show that dimers in the context of capsids form intradimer disulfides
relatively rapidly. Surprisingly, compared to reduced dimers, fully
oxidized dimers assembled slower and into capsids that were morphologically
similar but less stable. We hypothesize that oxidized protein adopts
a geometry (or constellation of geometries) that is unfavorable for
capsid assembly, resulting in weaker dimer–dimer interactions
as well as slower assembly kinetics. Our results suggest that structural
flexibility at the core protein intradimer interface is essential
for regulating capsid assembly and stability. We further suggest that
capsid destabilization by the C61–C61 disulfide has a regulatory
function to support capsid disassembly and release of the viral genome.