title: Visualization of a 4-helix bundle in the hepatitis B virus capsid by cryo-electron microscopy.
abstract: Despite the development of vaccines, the hepatitis B virus remains a major cause of human liver disease. The virion consists of a lipoprotein envelope surrounding an icosahedral capsid composed of dimers of a 183-residue protein, 'core antigen' (HBcAg). Knowledge of its structure is important for the design of antiviral drugs, but it has yet to be determined. Residues 150-183 are known to form a protamine-like domain required for packaging RNA, and residues 1-149 form the 'assembly domain' that polymerizes into capsids and, unusually for a capsid protein, is highly alpha-helical. Density maps calculated from cryo-electron micrographs show that the assembly domain dimer is T-shaped: its stem constitutes the dimer interface and the tips of its arms make the polymerization contacts. By refining the procedures used to calculate the map, we have extended the resolution to 9 A, revealing major elements of secondary structure. In particular, the stem, which protrudes as a spike on the capsid's outer surface, is a 4-helix bundle, formed by the pairing of alpha-helical hairpins from both subunits.
authors.affiliation: Laboratory of Structural Biology, National Institute of Arthritis, Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: J F
authors.initials: JF
authors.lastname: Conway
authors.forename: N
authors.initials: N
authors.lastname: Cheng
authors.forename: A
authors.initials: A
authors.lastname: Zlotnick
authors.forename: P T
authors.initials: PT
authors.lastname: Wingfield
authors.forename: S J
authors.initials: SJ
authors.lastname: Stahl
authors.forename: A C
authors.initials: AC
authors.lastname: Steven
mesh_terms: D002213:Capsid / Q000737:chemistry / Q000648:ultrastructure*; D019281:Dimerization; D004926:Escherichia coli; D005615:Freezing; D006512:Hepatitis B Core Antigens / Q000737:chemistry / Q000648:ultrastructure*; D007091:Image Processing, Computer-Assisted; D008854:Microscopy, Electron / Q000379:methods*; D008958:Models, Molecular; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000737:chemistry / Q000648:ultrastructure
chemical_list: D006512:Hepatitis B Core Antigens; D011994:Recombinant Proteins