title: Biophysical characterization of hepatitis C virus core protein: implications for interactions within the virus and host.
abstract: A primary function of the hepatitis C virus (HCV) core protein is to package the viral genome within a nucleocapsid. In addition, core protein has been shown to interact with more than a dozen cellular proteins, and these interactions have been suggested to play critical roles in HCV pathogenesis. A more complete knowledge of the biophysical properties of the core protein may help to clarify its role in HCV pathogenesis and nucleocapsid assembly and provide a basis for the development of novel anti-HCV therapies. Here we report that recombinant mature core protein exists as a large multimer in solution under physiological conditions. Far-UV circular dichroism (CD) experiments showed that the mature core protein contains stable secondary structure. Studies with truncated core protein demonstrated that the C-terminal region of the core protein is critical for its folding and oligomerization. Intrinsic fluorescence spectroscopy and near-UV CD analysis indicated that the tryptophan-rich region (residues 76-113) is largely solvent-exposed and not likely responsible for multimerization of the mature core protein in vitro.
authors.affiliation: Department of Human Biological Chemistry, University of Texas Medical Branch, Galveston, TX 77555, USA.
authors.forename: Meghan
authors.initials: M
authors.lastname: Kunkel
authors.forename: Stanley J
authors.initials: SJ
authors.lastname: Watowich
mesh_terms: D002942:Circular Dichroism; D004220:Disulfides; D006526:Hepatitis C / Q000503:physiopathology; D018936:Hepatitis C Antigens / Q000737:chemistry / Q000648:ultrastructure; D006801:Humans; D046911:Macromolecular Substances; D008854:Microscopy, Electron; D008970:Molecular Weight; D013050:Spectrometry, Fluorescence; D014758:Viral Core Proteins / Q000737:chemistry* / Q000648:ultrastructure
chemical_list: D004220:Disulfides; D018936:Hepatitis C Antigens; D046911:Macromolecular Substances; D014758:Viral Core Proteins; C069130:nucleocapsid protein, Hepatitis C virus