engleski

STRUCTURE OF THE HEPATITIS B VIRUS CORE PROTEIN AND ITS INTERACTIONS WITH THE ENVELOPE PROTEINS

The hepatitis B virus (HBV) is a small, enveloped virus, member of the Hepadna viral family with unusual, partially double-stranded DNA genome. The predominant viral core form in vivo is 34 nm particle with T=4 icosahedral symmetry, constructed from 240 copies of the HBV core protein (HBc). The HBV core protein is 22 kD, 183-185 amino acids long protein with primary structure composed of two structurally and functionally distinct regions. The N-terminal region is 149-151 amino acids long assembly domain, capable of directing the correct fold of the core monomer. The 34 residues long C-terminal domain, completely dispensable for core assembly, is extremely rich in conserved arginine (R) residues and takes part in the viral pre-genome/RT binding and encapsidation. The cryo-electron microscopy and X-ray crystallography studies on the HBV core particles revealed an unexpectedly large helical protein structure, with the long α helical hairpin dominating the entire monomer fold. The amphipatic helical hairpins of two core monomers interact forming the compact dimer, whose interface covers the large hydrophobic surfaces of the individual monomers. The hydrophobic interactions thus constitute the major driving force for the dimer assembly and account for the assembled core stability. The four helix bundle of the dimer is a distinct core structural feature, with important functional role. This is well observed upon the maturation of the immature pre-genomic RNA/RT complex-containing HBV core particle. The unusual reverse transcription of the pre-genomic RNA generates the partially dsDNA of mature virion, the event which induces the sequence of the conformational changes in the dimer core protein with which the nucleic acid interacts. The changes are best observable on the four-helix bundle dimer structure and insure the generating of the dimer hydrophobic pocket on core surface which subsequently interacts with the pre-S1 region of the HBV S envelope protein. This mechanism ensures that only the mature viral core particles (with encapsidated dsDNA) are capable of the successful envelopment and budding at an intracellular hepatocyte membrane.

HEPATITIS B VIRUS; CORE PROTEIN; ENVELOPE PROTEINS; INTERACTIONS

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