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PMID:8189513
| Citation |
Failla, C, Tomei, L and De Francesco, R (1994) Both NS3 and NS4A are required for proteolytic processing of hepatitis C virus nonstructural proteins. J. Virol. 68:3753-60 |
|---|---|
| Abstract |
The proteolytic cleavages at the NS3-NS4A, NS4A-NS4B, NS4B-NS5A, and NS5A-NS5B junctions of hepatitis C virus (HCV) polyprotein are effected by the virus-encoded serine protease contained within NS3. Using transient expression in HeLa cells of cDNA fragments that code for regions of the HCV polyprotein, we studied whether viral functions other than NS3 are required for proteolytic processing at these sites. We found that, in addition to NS3, a C-terminal 33-amino-acid sequence of the NS4A protein is required for cleavage at the NS3-NS4A and NS4B-NS5A sites and that it accelerates the rate of cleavage at the NS5A-NS5B junction. In addition, we show that NS4A can activate the NS3 protease when supplied in trans. Our data suggest that HCV NS4A may be the functional analog of flavivirus NS2B and pestivirus p10 proteins. |
| Links | |
| Keywords |
Amino Acid Sequence; Binding Sites; Enzyme Activation; HeLa Cells; Hepacivirus/genetics; Hepacivirus/metabolism; Humans; Molecular Sequence Data; Protein Precursors/genetics; Protein Precursors/metabolism; Protein Processing, Post-Translational; Serine Endopeptidases/metabolism; Viral Nonstructural Proteins/genetics; Viral Nonstructural Proteins/metabolism |
| edit table |
Significance
Annotations
| Gene product | Qualifier | GO Term | Evidence Code | with/from | Aspect | Extension | Notes | Status |
|---|---|---|---|---|---|---|---|---|
| GO:0008236: serine-type peptidase activity |
ECO:0000315: |
F |
Figure 4. Demonstrates replacing the catalytic serine with an alanine results in a loss of self-cleavage. |
complete | ||||
| GO:0097264: self proteolysis |
ECO:0000314: |
P |
Figure 4. Demonstrates the peptide is capable of undergoing self-cleavage. |
complete | ||||
|
enables |
GO:0008236: serine-type peptidase activity |
ECO:0000315: mutant phenotype evidence used in manual assertion |
F |
Seeded From UniProt |
complete | |||
|
involved_in |
GO:0097264: self proteolysis |
ECO:0000314: direct assay evidence used in manual assertion |
P |
Seeded From UniProt |
complete | |||
Notes
See also
References
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