Conformational changes accompanying self-assembly of the hepatitis C virus core protein.
Although a number of recent studies have suggested that the function of the hepatitis C virus (HCV) core protein may be both to package the viral genome and to modulate host cellular processes, little is known of the structure of the core protein necessary to accomplish these functions. Using in vitro assembled particles that mimic essential features of native HCV nucleocapsids, we report the earliest structural information of the HCV core protein and its nucleocapsid. The core protein is proteinase-resistant when assembled into nucleocapsid-like particles or complexed with nucleic acid in vitro. In contrast, the highly basic amino terminus of the free core protein is sensitive to proteolytic digestion. The hydrophobic carboxyl-terminal region of the core protein stabilizes the structure of the free core protein but is not required to stabilize core protein assembled into nucleocapsid-like particles or complexed to nucleic acid. Significantly, the carboxyl-terminal region is sufficient, but not necessary, to fold the core protein into a stable structure. These data are consistent with a model of a partially flexible HCV core protein that undergoes extensive conformational changes upon binding to nucleic acid and assembling into nucleocapsid particles. In addition, the susceptibility of nucleocapsid particles to RNase digestion suggests that RNA-core interactions may stabilize HCV nucleocapsids.
Kunkel
Meghan
M
Department of Human Biological Chemistry & Genetics, University of Texas Medical Branch, Galveston, Texas 77555, USA.
Watowich
Stanley J
SJ
D002918:Chymotrypsin / Q000378:metabolism; D016174:Hepacivirus / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D019251:Nucleocapsid; D011487:Protein Conformation; D012343:RNA, Transfer / Q000378:metabolism; D012367:RNA, Viral / Q000378:metabolism; D012260:Ribonucleases / Q000378:metabolism; D014357:Trypsin / Q000378:metabolism; D014758:Viral Core Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014771:Virion; D019065:Virus Assembly / Q000502:physiology*
D012367:RNA, Viral; D014758:Viral Core Proteins; C069130:nucleocapsid protein, Hepatitis C virus; D012343:RNA, Transfer; D012260:Ribonucleases; D002918:Chymotrypsin; D014357:Trypsin