title: Identification and characterization of peptides that interact with hepatitis B virus via the putative receptor binding site.
abstract: A direct involvement of the PreS domain of the hepatitis B virus (HBV) large envelope protein, and in particular amino acid residues 21 to 47, in virus attachment to hepatocytes has been suggested by many previous studies. Several PreS-interacting proteins have been identified. However, they share few common sequence motifs, and a bona fide cellular receptor for HBV remains elusive. In this study, we aimed to identify PreS-interacting motifs and to search for novel HBV-interacting proteins and the long-sought receptor. PreS fusion proteins were used as baits to screen a phage display library of random peptides. A group of PreS-binding peptides were obtained. These peptides could bind to amino acids 21 to 47 of PreS1 and shared a linear motif (W1T2X3W4W5) sufficient for binding specifically to PreS and viral particles. Several human proteins with such a motif were identified through BLAST search. Analysis of their biochemical and structural properties suggested that lipoprotein lipase (LPL), a key enzyme in lipoprotein metabolism, might interact with PreS and HBV particles. The interaction of HBV with LPL was demonstrated by in vitro binding, virus capture, and cell attachment assays. These findings suggest that LPL may play a role in the initiation of HBV infection. Identification of peptides and protein ligands corresponding to LPL that bind to the HBV envelope will offer new therapeutic strategies against HBV infection.
authors.affiliation: State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, and Ruijin Hospital, Department of Infectious Diseases, Shanghai, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Deng
authors.forename: Jian-wei
authors.initials: JW
authors.lastname: Zhai
authors.forename: Marie-Louise
authors.initials: ML
authors.lastname: Michel
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.forename: Jun
authors.initials: J
authors.lastname: Qin
authors.forename: Yu-ying
authors.initials: YY
authors.lastname: Kong
authors.forename: Xin-xin
authors.initials: XX
authors.lastname: Zhang
authors.forename: Agata
authors.initials: A
authors.lastname: Budkowska
authors.forename: Pierre
authors.initials: P
authors.lastname: Tiollais
authors.forename: Yuan
authors.initials: Y
authors.lastname: Wang
authors.forename: You-hua
authors.initials: YH
authors.lastname: Xie
mesh_terms: D020816:Amino Acid Motifs; D001665:Binding Sites; D002460:Cell Line; D006514:Hepatitis B Surface Antigens / Q000378:metabolism*; D006515:Hepatitis B virus / Q000502:physiology*; D022781:Hepatocytes / Q000821:virology*; D006801:Humans; D008071:Lipoprotein Lipase / Q000378:metabolism*; D019151:Peptide Library; D011485:Protein Binding; D011498:Protein Precursors / Q000378:metabolism*; D011991:Receptors, Virus / Q000032:analysis* / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D053585:Virus Attachment
chemical_list: D006514:Hepatitis B Surface Antigens; D019151:Peptide Library; D011498:Protein Precursors; D011991:Receptors, Virus; D011993:Recombinant Fusion Proteins; C050806:presurface protein 1, hepatitis B surface antigen; D008071:Lipoprotein Lipase