title: Endonexin II, present on human liver plasma membranes, is a specific binding protein of small hepatitis B virus (HBV) envelope protein.
abstract: Binding of viral envelope proteins to specific receptors on human hepatocytes is considered to be an important step in HBV infection. In this study, we demonstrate that a 34-kDa human liver plasma membrane protein specifically binds to small HBsAg in a Ca(2+)-dependent manner. By partial amino acid sequence analysis of preparatively isolated 34-kDa protein comigrating with HBsAg-binding protein obtained from binding assay on IEF/SDS-PAGE, we have identified this HBsAg-binding protein as Endonexin II (E-II). Native human liver E-II inhibits binding of HBsAg to intact human hepatocytes and shows specific binding to small HBsAg. This binding can be inhibited by human liver plasma membrane proteins, recombinant E-II, or anti-E-II antibodies. Despite 90% sequence homology, rat liver E-II does not bind to small HBsAg and does not inhibit significantly (less than 20%) binding of HBsAg to intact hepatocytes. Cross-linking of small HBsAg and radiolabeled human liver E-II resulted in a specific additional protein complex on PAGE with an apparent molecular weight of 90 kDa, corresponding to a complex of E-II and small HBsAg with a ratio of 2 to 1 or 1 to 2. These findings indicate that E-II, found in human liver, is a specific HBsAg-binding protein and might play an important role in the initiation of HBV infection.
authors.affiliation: Division of Liver and Pancreatic Diseases, University Hospital Gasthuisberg, Leuven, Belgium.
authors.forename: K
authors.initials: K
authors.lastname: Hertogs
authors.forename: W P
authors.initials: WP
authors.lastname: Leenders
authors.forename: E
authors.initials: E
authors.lastname: Depla
authors.forename: W C
authors.initials: WC
authors.lastname: De Bruin
authors.forename: L
authors.initials: L
authors.lastname: Meheus
authors.forename: J
authors.initials: J
authors.lastname: Raymackers
authors.forename: H
authors.initials: H
authors.lastname: Moshage
authors.forename: S H
authors.initials: SH
authors.lastname: Yap
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017304:Annexin A5 / Q000302:isolation & purification / Q000378:metabolism* / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D002462:Cell Membrane / Q000378:metabolism; D003432:Cross-Linking Reagents; D015686:Gene Products, env / Q000187:drug effects / Q000378:metabolism*; D006514:Hepatitis B Surface Antigens / Q000187:drug effects / Q000378:metabolism*; D006515:Hepatitis B virus / Q000378:metabolism*; D006801:Humans; D008099:Liver / Q000378:metabolism*; D008969:Molecular Sequence Data; D051381:Rats; D011991:Receptors, Virus / Q000187:drug effects / Q000302:isolation & purification / Q000378:metabolism*; D011994:Recombinant Proteins / Q000187:drug effects / Q000378:metabolism; D017421:Sequence Analysis
chemical_list: D017304:Annexin A5; D003432:Cross-Linking Reagents; D015686:Gene Products, env; D006514:Hepatitis B Surface Antigens; D011991:Receptors, Virus; D011994:Recombinant Proteins; D002118:Calcium