The acidic sequence of the NS4A cofactor regulates ATP hydrolysis by the HCV NS3 helicase
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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.
KeywordsATPase Activity West Nile Virus Dengue Virus Japanese Encephalitis Virus Yellow Fever Virus
This study was supported by NIH grants RR020843 and AI055789 (AYS).
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