title: Protein X of hepatitis B virus: origin and structure similarity with the central domain of DNA glycosylase.
abstract: Orthohepadnavirus (mammalian hosts) and avihepadnavirus (avian hosts) constitute the family of Hepadnaviridae and differ by their capability and inability for expression of protein X, respectively. Origin and functions of X are unclear. The evolutionary analysis at issue of X indicates that present strains of orthohepadnavirus started to diverge about 25,000 years ago, simultaneously with the onset of avihepadnavirus diversification. These evolutionary events were preceded by a much longer period during which orthohepadnavirus developed a functional protein X while avihepadnavirus evolved without X. An in silico generated 3D-model of orthohepadnaviral X protein displayed considerable similarity to the tertiary structure of DNA glycosylases (key enzymes of base excision DNA repair pathways). Similarity is confined to the central domain of MUG proteins with the typical DNA-binding facilities but without the capability of DNA glycosylase enzymatic activity. The hypothetical translation product of a vestigial X reading frame in the genome of duck hepadnavirus could also been folded into a DNA glycosylase-like 3D-structure. In conclusion, the most recent common ancestor of ortho- and avihepadnavirus carried an X sequence with orthology to the central domain of DNA glycosylase.
authors.affiliation: Laboratory of Experimental Virology, Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. f.j.vanhemert@amc.uva.nl
authors.forename: Formijn J
authors.initials: FJ
authors.lastname: van Hemert
authors.forename: Maarten A A
authors.initials: MA
authors.lastname: van de Klundert
authors.forename: Vladimir V
authors.initials: VV
authors.lastname: Lukashov
authors.forename: Neeltje A
authors.initials: NA
authors.lastname: Kootstra
authors.forename: Ben
authors.initials: B
authors.lastname: Berkhout
authors.forename: Hans L
authors.initials: HL
authors.lastname: Zaaijer
mesh_terms: D000818:Animals; D017917:Avihepadnavirus / Q000201:enzymology; D045647:DNA Glycosylases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D017918:Orthohepadnavirus / Q000201:enzymology; D017433:Protein Structure, Secondary; D015534:Trans-Activators / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D054334:Viral Regulatory and Accessory Proteins
chemical_list: D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein; D045647:DNA Glycosylases