Satoh S, Tanji Y, Hijikata M, Kimura K, Shimotohno K
Department of Applied Biological Science, Faculty of Science and Technology, Science University of Tokyo, Japan.
J Virol. 1995 Jul;69(7):4255-60. doi: 10.1128/JVI.69.7.4255-4260.1995.
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.
丙型肝炎病毒蛋白是由病毒前体多蛋白经蛋白水解加工产生的，该前体多蛋白由病毒基因组最大的开放阅读框编码。非结构病毒多蛋白的加工需要非结构蛋白3（NS3）中存在的病毒丝氨酸型蛋白酶。只有当NS4A存在时，NS3才介导NS4B和NS5A之间连接点的切割。NS4A被认为是一种辅助因子，可提高丙型肝炎病毒蛋白产生细胞中NS3的切割效率。稳定的NS3-NS4A复合物形成需要NS3的N端22个氨基酸残基。这种相互作用有助于NS3产物的稳定，并提高NS4B/5A位点的切割效率。与大肠杆菌二氢叶酸还原酶融合的N端22个氨基酸残基也与NS4A形成稳定的复合物。即使在存在NS4A的情况下，缺少N端22个氨基酸残基的NS3衍生物在NS4B/5A位点的切割活性也显著降低。这些数据表明，通过NS3的22个氨基酸残基与NS4A的相互作用对于NS3对NS4B/5A位点的NS4A依赖性加工至关重要。
