The Stalk and 1B Domains Are Required for Porcine Deltacoronavirus Helicase NSP13 to Separate the Double-Stranded Nucleic Acids, and the Deletion of the ZBD Impairs This Activity

猪δ冠状病毒解旋酶NSP13需要茎部结构域和1B结构域才能分离双链核酸,而ZBD的缺失会损害这种活性。

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Abstract

The nonstructural protein 13 (NSP13) of PDCoV is a highly conservative helicase and plays key roles in viral replication. NSP13 contains a zinc-binding domain (ZBD), a helical Stalk domain, a beta-barrel 1B domain, and a core helicase domain. However, the specific functions of these domains of PDCoV NSP13 remain largely unknown. Here, we expressed and purified the wild-type NSP13(WT) and various mutants with domain deletions, and the activities of these proteins were analyzed using multiple methods. We found that NSP13(ΔZBD) possessed the abilities to hydrolyze ATP and unwind double-stranded nucleic acids, but the unwinding efficiency was lower than that of NSP13(WT). In contrast, NSP13(ΔZBD-Stalk), NSP13(Δ1B), and NSP13(ΔZBD-Stalk-1B) all lost their unwinding activity, but not their ATPase activity. These results revealed that the deletion of the ZBD impaired the unwinding activity of PDCoV helicase NSP13, and the Stalk and 1B domains were critical for NSP13 to separate the duplexes. The identification of the roles of each domain in this study was helpful to gain an in-depth understanding of the overall functions of helicase NSP13, providing a theoretical basis for the development of antiviral drugs targeting helicase.

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