Endonexin II, present on human liver plasma membranes, is a specific binding protein of small hepatitis B virus (HBV) envelope protein.
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.
Hertogs
K
K
Division of Liver and Pancreatic Diseases, University Hospital Gasthuisberg, Leuven, Belgium.
Leenders
W P
WP
Depla
E
E
De Bruin
W C
WC
Meheus
L
L
Raymackers
J
J
Moshage
H
H
Yap
S H
SH
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
D017304:Annexin A5; D003432:Cross-Linking Reagents; D015686:Gene Products, env; D006514:Hepatitis B Surface Antigens; D011991:Receptors, Virus; D011994:Recombinant Proteins; D002118:Calcium