Hepatitis B virus is a major human pathogen that consists of a viral genome
surrounded by an icosahedrally ordered core protein and a polymorphic, lipidic
envelope that is densely packed with surface proteins. A point mutation in the
core protein in which a phenylalanine at position 97 is exchanged for a smaller
leucine leads to premature envelopment of the capsid before the genome
maturation is fully completed. We have used electron cryo-microscopy and image
processing to investigate how the point mutation affects the structure of the
capsid at 2.6- to 2.8 Å-resolution. We found that in the mutant the smaller
side chain at position 97 is displaced, increasing the size of an adjacent
pocket in the center of the spikes of the capsid. In the mutant, this pocket is
filled with an unknown density. Phosphorylation of serine residues in the
unresolved C-terminal domain of the mutant leaves the structure of the ordered
capsid largely unchanged. However, we were able to resolve several previously
unresolved residues downstream of proline 144 that precede the
phosphorylation-sites. These residues pack against the neighboring subunits and
increase the inter-dimer contact suggesting that the C-termini play an important
role in capsid stabilization and provide a much larger interaction interface
than previously observed.
