Folding and assembly of hepatitis B virus core protein: a new model proposal.
Hepatitis B core antigen has been intensively studied. Recently, cryoelectron microscopy studies have determined the structure of human and duck hepatitis B virus nucleocapsids at low resolution. Both viruses assemble into core particles of two sizes with icosahedral dimer-clustered 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 mammalian and avian isolates and secondary structure predictions. The 54% alpha-helical conformation predicted is in good agreement with CD results reporting 53-71% content of alpha-helices. Despite the sequence divergence of mammalian and avian proteins, the secondary structure prediction of both shows a high degree of coincidence, according to the multiple sequence alignment. The proposed fold of HBc monomers is built from five alpha-helices. In dimers, pairs of two of those helices conform the protruding domain. The model also suggests the convergence of the region preceding the protamine domain around the sixfold symmetry axes. The model gives answers to most of the standing questions concerning the nucleocapsid assembly and antigenic behavior of HBc protein.
Bringas
R
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Center for Genetic Engineering and Biotechnology, Havana, Cuba.
D000595:Amino Acid Sequence; D000818:Animals; D017124:Conserved Sequence; D006512:Hepatitis B Core Antigens / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006515:Hepatitis B virus / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017386:Sequence Homology, Amino Acid; D014758:Viral Core Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
D006512:Hepatitis B Core Antigens; D014758:Viral Core Proteins