title: Determination of the fold of the core protein of hepatitis B virus by electron cryomicroscopy.
abstract: Hepatitis B virus, a major human pathogen with an estimated 300 million carriers worldwide, can lead to cirrhosis and liver cancer in cases of chronic infection. The virus consists of an inner nucleocapsid or core, surrounded by a lipid envelope containing virally encoded surface proteins. The core protein, when expressed in bacteria, assembles into core shell particles, closely resembling the native core of the virus. Here we use electron cryomicroscopy to solve the structure of the core protein to 7.4 A resolution. Images of about 6,400 individual particles from 34 micrographs at different levels of defocus were combined, imposing icosahedral symmetry. The three-dimensional map reveals the complete fold of the polypeptide chain, which is quite unlike previously solved viral capsid proteins and is largely alpha-helical. The dimer clustering of subunits produces spikes on the surface of the shell, which consist of radial bundles of four long alpha-helices. Our model implies that the sequence corresponding to the immunodominant region of the core protein lies at the tip of the spike and also explains other properties of the core protein.
authors.affiliation: Medical Research Council Laboratory of Molecular Biology, Cambridge, UK.
authors.forename: B
authors.initials: B
authors.lastname: Böttcher
authors.forename: S A
authors.initials: SA
authors.lastname: Wynne
authors.forename: R A
authors.initials: RA
authors.lastname: Crowther
mesh_terms: D002213:Capsid / Q000737:chemistry / Q000648:ultrastructure; D002460:Cell Line; D019281:Dimerization; 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; D017510:Protein Folding; D011994:Recombinant Proteins / Q000737:chemistry / Q000648:ultrastructure
chemical_list: D006512:Hepatitis B Core Antigens; D011994:Recombinant Proteins