DETERMINATION OF THE FOLD OF THE CORE PROTEIN OF HEPATITIS-B VIRUS KYELECTRON CRYOMICROSCOPY

Hepatitis B virus, a major human pathogen with an estimated 300 millio n carriers worldwide, can lead to cirrhosis and liver cancer in cases of chronic infection. The virus consists of an inner nucleocapsid or c ore, surrounded by a lipid envelope containing virally encoded surface proteins. The core protein, when expressed in bacteria, assembles int o core shell particles, closely resembling the native core of the viru s. Here we use electron cryomicroscopy to solve the structure of the c ore protein to 7.4 Angstrom resolution. Images of about 6,400 individu al particles from 34 micrographs at different levels of defocus were c ombined, imposing icosahedral symmetry. The three-dimensional map reve als 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. Ou r model implies that the sequence corresponding to the immunodominant region of the core protein lies at the tip of the spike and also expla ins other properties of the core protein.