The acidic sequence of the NS4A cofactor regulates ATP hydrolysis by the HCV NS3 helicase
- First Online:
In flaviviruses and hepatitis C virus (HCV), the NS3 gene encodes the N-terminal protease (NS3pro) and the C-terminal helicase (NS3hel). In HCV, the downstream NS4A is required for the NS3pro activity and exhibits a conserved EFDEMEE motif. To identify the role of this motif, we compared the ATPase and helicase activities of NS3 alone with those of the NS3-NS4A constructs. Our results suggest that the EFDEMEE motif is essential for regulating the ATPase activity of NS3hel. It is likely that this motif interferes with the ATP-binding site of NS3hel. It is becoming clear that NS4A functions as a cofactor of both proteinase and helicase in HCV.
- 14.Mackintosh SG, Lu JZ, Jordan JB, Harrison MK, Sikora B, Sharma SD, Cameron CE, Raney KD, Sakon J (2006) Structural and biological identification of residues on the surface of NS3 helicase required for optimal replication of the hepatitis C virus. J Biol Chem 281:3528–3535CrossRefPubMedGoogle Scholar
- 17.Assenberg R, Mastrangelo E, Walter TS, Verma A, Milani M, Owens RJ, Stuart DI, Grimes JM, Mancini EJ (2009) Crystal structure of a novel conformational state of the flavivirus NS3 protein: implications for polyprotein processing and viral replication. J Virol 83:12895–12906CrossRefPubMedGoogle Scholar