title: The hepatitis B virus core protein intradimer interface modulates capsid assembly and stability.
abstract: During 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.
authors.affiliation: Department of Molecular and Cellular Biochemistry, Indiana University , Bloomington, Indiana 47405, United States.
authors.forename: Lisa
authors.initials: L
authors.lastname: Selzer
authors.forename: Sarah P
authors.initials: SP
authors.lastname: Katen
authors.forename: Adam
authors.initials: A
authors.lastname: Zlotnick
mesh_terms: D000595:Amino Acid Sequence; D002213:Capsid / Q000737:chemistry*; D019281:Dimerization; D006515:Hepatitis B virus / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D017386:Sequence Homology, Amino Acid; D013816:Thermodynamics; D014758:Viral Core Proteins / Q000737:chemistry*
chemical_list: D014758:Viral Core Proteins
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