title: Homotypic interaction and multimerization of hepatitis C virus core protein.
abstract: Hepatitis C virus (HCV) core protein constitutes a viral nucleocapsid and may possess multiple functions. In this study, we demonstrated the homotypic interaction and multimerization of HCV core protein in vitro and in vivo. By using a yeast two-hybrid system, we showed that the amino-terminal hydrophilic portion (amino acids 1-115) of the core protein could interact with itself. Deletion analysis mapped the interacting domain within amino acid residues 36-91. The homotypic interaction of the core protein was also confirmed by in vitro protein-protein blotting assay using the recombinant HCV core proteins and by its binding to the glutathione S-transferase core fusion protein. The biological significance of the core protein self-interactions was demonstrated by the detection of multimeric forms of the core protein in mammalian cells. The domain responsible for multimerization was determined to be within the amino-terminal hydrophilic region (amino acids 1-115). Both the membrane-bound and the free core proteins exist in dimeric and multimeric forms, suggesting that multimerization of the HCV core protein occurred at an early stage of viral assembly and that the multimer forms may be involved in multiple functions of the core protein.
authors.affiliation: Howard Hughes Medical Institute,University of Southern California School of Medicine, Los Angeles, California, 90033, USA.
authors.forename: M
authors.initials: M
authors.lastname: Matsumoto
authors.forename: S B
authors.initials: SB
authors.lastname: Hwang
authors.forename: K S
authors.initials: KS
authors.lastname: Jeng
authors.forename: N
authors.initials: N
authors.lastname: Zhu
authors.forename: M M
authors.initials: MM
authors.lastname: Lai
mesh_terms: D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D016174:Hepacivirus / Q000378:metabolism*; D008322:Mammals; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae; D014758:Viral Core Proteins / Q000378:metabolism*
chemical_list: D011993:Recombinant Fusion Proteins; D014758:Viral Core Proteins; C069130:nucleocapsid protein, Hepatitis C virus