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PMID:7769685

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Citation

Satoh, S, Tanji, Y, Hijikata, M, Kimura, K and Shimotohno, K (1995) The N-terminal region of hepatitis C virus nonstructural protein 3 (NS3) is essential for stable complex formation with NS4A. J. Virol. 69:4255-60

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/5A 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/5A 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.

Links

PubMed PMC189163

Keywords

Base Sequence; Molecular Sequence Data; Mutation; Peptide Fragments/physiology; Serine Endopeptidases/physiology; Viral Nonstructural Proteins/physiology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HCVH:POLG

involved_in

GO:0045862: positive regulation of proteolysis

ECO:0000314: direct assay evidence used in manual assertion

P

has_regulation_target:(UniProtKB:P27958:PRO_0000037573)

Seeded From UniProt

complete

HCVH:POLG

involved_in

GO:0048524: positive regulation of viral process

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HCVH:POLG

part_of

GO:0044164: host cell cytosol

ECO:0000315: mutant phenotype evidence used in manual assertion

C

Seeded From UniProt

complete

HCVH:POLG

part_of

GO:0033644: host cell membrane

ECO:0000315: mutant phenotype evidence used in manual assertion

C

Seeded From UniProt

complete

Notes

See also

References

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