FOLDING AND ASSEMBLY OF HEPATITIS-B VIRUS CORE PROTEIN - A NEW MODEL PROPOSAL

Hepatitis B core antigen has been intensively studied. Recently, cryoe lectron microscopy studies have determined the structure of human and duck hepatitis B virus nucleocapsids at low resolution. Both viruses a ssemble into core particles of two sizes with icosahedral dimer-cluste red T = 3 and T = 4 symmetries. Both capsids present tightly clustered dimers composed of a shell and a protruding domain. The present work introduces a model for HBc folding, dimer formation, and assembly. The model is based in multiple alignments of HBc sequences from 20 mammal ian and avian isolates and secondary structure predictions. The 54% al pha-helical conformation predicted is in good agreement with CD result s reporting 53-71% content of alpha-helices. Despite the sequence dive rgence of mammalian and avian proteins, the secondary structure predic tion of both shows a high degree of coincidence, according to the mult iple sequence alignment. The proposed fold of HBc monomers is built fr om five a-helices. In dimers, pairs of two of those helices conform th e protruding domain. The model also suggests the convergence of the re gion preceding the protamine domain around the sixfold symmetry axes. The model gives answers to most of the standing questions concerning t he nucleocapsid assembly and antigenic behavior of HBc protein. (C) 19 97 Academic Press.