Conformational changes accompanying self-assembly of the hepatitis C virus core protein

Meghan Kunkel, Stanley Watowich

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)239-245
Number of pages7
JournalVirology
Volume294
Issue number2
DOIs
StatePublished - 2002

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Nucleocapsid
Proteins
Nucleic Acids
Hepacivirus
Digestion
Viral Genome
Ribonucleases
Hepatitis C virus nucleocapsid protein
Peptide Hydrolases
RNA

ASJC Scopus subject areas

  • Virology
  • Infectious Diseases

Cite this

Conformational changes accompanying self-assembly of the hepatitis C virus core protein. / Kunkel, Meghan; Watowich, Stanley.

In: Virology, Vol. 294, No. 2, 2002, p. 239-245.

Research output: Contribution to journalArticle

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