title: Serine phosphoacceptor sites within the core protein of hepatitis B virus contribute to genome replication pleiotropically.
abstract: The core protein of hepatitis B virus can be phosphorylated at serines 155, 162, and 170. The contribution of these serine residues to DNA synthesis was investigated. Core protein mutants were generated in which each serine was replaced with either alanine or aspartate. Aspartates can mimic constitutively phosphorylated serines while alanines can mimic constitutively dephosphorylated serines. The ability of these mutants to carry out each step of DNA synthesis was determined. Alanine substitutions decreased the efficiency of minus-strand DNA elongation, primer translocation, circularization, and plus-strand DNA elongation. Aspartate substitutions also reduced the efficiency of these steps, but the magnitude of the reduction was less. Our findings suggest that phosphorylated serines are required for multiple steps during DNA synthesis. It has been proposed that generation of mature DNA requires serine dephosphorylation. Our results suggest that completion of rcDNA synthesis requires phosphorylated serines.
authors.affiliation: McArdle Laboratory for Cancer Research, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, United States of America.
authors.forename: Eric B
authors.initials: EB
authors.lastname: Lewellyn
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Loeb
mesh_terms: D000595:Amino Acid Sequence; D020134:Catalytic Domain / Q000235:genetics / Q000502:physiology; D004261:DNA Replication / Q000502:physiology*; D004279:DNA, Viral / Q000235:genetics / Q000378:metabolism; D016679:Genome, Viral / Q000235:genetics; D056945:Hep G2 Cells; D006512:Hepatitis B Core Antigens / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D006515:Hepatitis B virus / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D006801:Humans; D008957:Models, Genetic; D008969:Molecular Sequence Data; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D017385:Sequence Homology; D012694:Serine / Q000235:genetics / Q000378:metabolism*; D014758:Viral Core Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication / Q000502:physiology
chemical_list: D004279:DNA, Viral; D006512:Hepatitis B Core Antigens; D014758:Viral Core Proteins; D012694:Serine; D017346:Protein Serine-Threonine Kinases