The N-terminal region of hepatitis C virus nonstructural protein 3 (NS3) is essential for stable complex formation with NS4A

Shinya Satoh, Y. Tanji, M. Hijikata, K. Kimura, K. Shimotohno

Research output: Contribution to journalArticle

86 Citations (Scopus)

Abstract

Hepatitis C virus proteins are produced by proteolytic processing of the viral precursor polyprotein that is encoded in the largest open reading frame of the viral genome. Processing of the nonstructural viral polyprotein requires the viral serine-type proteinase present in nonstructural protein 3 (NS3). The cleavage of the junction between NS4B and NS5A is mediated by NS3 only when NS4A is present. NS4A is thought to be a cofactor that enhances the cleavage efficiency of NS3 in hepatitis C virus protein-producing cells. Stable NS3-NS4A complex formation required the N-terminal 22 amino acid residues of NS3. This interaction contributed to stabilization of the NS3 product as well as increased the efficiency of cleavage at the NS4B/SA site. The N-terminal 22 amino acid residues fused to Escherichia coli dihydrofolate reductase also formed a stable complex with NS4A. NS3 derivatives which lacked the N-terminal 22 amino acid residues showed drastically reduced cleavage activity at the NS4B/SA site even in the presence of NS4A. These data suggested that the interaction with NS4A through the 22 amino acid residues of NS3 is primarily important for the NS4A-dependent processing of the NS4B/5A site by NS3.

Original languageEnglish
Pages (from-to)4255-4260
Number of pages6
JournalJournal of Virology
Volume69
Issue number7
Publication statusPublished - 1995
Externally publishedYes

Fingerprint

Hepatitis C virus
Hepacivirus
Proteins
proteins
Amino Acids
Polyproteins
amino acids
dihydrofolate reductase
Tetrahydrofolate Dehydrogenase
Viral Genome
Serine Proteases
serine
Open Reading Frames
open reading frames
proteinases
Escherichia coli

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

The N-terminal region of hepatitis C virus nonstructural protein 3 (NS3) is essential for stable complex formation with NS4A. / Satoh, Shinya; Tanji, Y.; Hijikata, M.; Kimura, K.; Shimotohno, K.

In: Journal of Virology, Vol. 69, No. 7, 1995, p. 4255-4260.

Research output: Contribution to journalArticle

Satoh, Shinya ; Tanji, Y. ; Hijikata, M. ; Kimura, K. ; Shimotohno, K. / The N-terminal region of hepatitis C virus nonstructural protein 3 (NS3) is essential for stable complex formation with NS4A. In: Journal of Virology. 1995 ; Vol. 69, No. 7. pp. 4255-4260.
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