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The acidic sequence of the NS4A cofactor regulates ATP hydrolysis by the HCV NS3 helicase

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Abstract

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.

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Acknowledgments

This study was supported by NIH grants RR020843 and AI055789 (AYS).

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Authors and Affiliations

  1. Inflammatory and Infectious Disease Center, Sanford-Burnham Medical Research Institute, 10901 North Torrey Pines Rd, La Jolla, CA, 92037, USA

    Sergey A. Shiryaev, Andrei V. Chernov, Tatiana N. Shiryaeva, Alexander E. Aleshin & Alex Y. Strongin

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  1. Sergey A. Shiryaev
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  2. Andrei V. Chernov
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  3. Tatiana N. Shiryaeva
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  4. Alexander E. Aleshin
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  5. Alex Y. Strongin
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Corresponding author

Correspondence to Alex Y. Strongin.

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Shiryaev, S.A., Chernov, A.V., Shiryaeva, T.N. et al. The acidic sequence of the NS4A cofactor regulates ATP hydrolysis by the HCV NS3 helicase. Arch Virol 156, 313–318 (2011). https://doi.org/10.1007/s00705-010-0838-2

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  • DOI: https://doi.org/10.1007/s00705-010-0838-2

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