A PROTEASE-SENSITIVE HINGE LINKING THE 2 DOMAINS OF THE HEPATITIS-B VIRUS CORE PROTEIN IS EXPOSED ON THE VIRAL CAPSID SURFACE

Core particles of hepatitis B virus are assembled from dimers of a sin gle 185-residue (subtype adw) viral capsid or core protein (P21.5) whi ch possesses two distinct domains: residues 1 to 144 form a minimal ca psid assembly domain, and the arginine-rich, carboxyl-terminal residue s 150 to 185 form a protamine-like domain that mediates nucleic acid b inding. Little is known about th topography of the p21.5 polypeptide w ithin either the p21.5 residues in dimers and capsids assembled from w ild-type and mutant hepatitis B virus core proteins in Xenopus oocytes and in vitro. The data reveal the protamine region to be accessible t o external reagents in p21.5 dimers but largely cryptic in wild-type c apsids. Strikingly, in capsids the only protease target region was a 9 -residue peptide covering p21.5 residues Glu-145 to Asp-153, which fal ls largely between the two core protein domains. By analogy with prote ase-sensitive interdomain regions in other proteins, we propose that t his peptide constitutes a hinge between the assembly and nucleic acid binding domains of p21.5. We further found that deletion or replacemen t of the terminal Cys-185 residue greatly increased surface exposure o f the protamine tails in capsids, suggesting that a known disulfide li nkage involving this residue tethers the protamine region inside the c ore particles. We propose that disruption of this disulfide linkage al lows the protamine region to appear transiently on the surface of the core particle.