Structural basis for the regulatory function of a complex zinc-binding domain in a replicative arterivirus helicase resembling a nonsense-mediated mRNA decay helicase

Deng, Zengqin; Lehmann, Kathleen C.; Li, Xiaorong; Feng, Chong; Wang, Guoqiang; Zhang, Qi; Qi, Xiaoxuan; Yu, Lin; Zhang, Xingliang; Feng, Wenhai; Wu, Wei; Gong, Peng; Tao, Ye; Posthuma, Clara C.; Snijder, Eric J.; Gorbalenya, Alexander E.; Chen, Zhongzhou

Despite its importance as a key replicative enzyme and antiviral drug target (39) , no 3D structural information has been reported for any nidovirus helicase. To understand the regulatory role of ZBD and the protein's interaction with nucleic acids, we characterized the structure of a helicase-competent derivative of EAV nsp10, alone and in complex with poly(dT). The multi-domain nsp10 includes the canonical 1A and 2A core domains of a SF1 helicase, a flexible accessory domain that is sensitive to nucleic acid binding, and a complex ZBD displaying a novel structural organization. Strikingly, the protein was found to bear structural resemblance to the eukaryotic Upf1 helicases, which are multi-domain proteins involved in RNA quality control, including nonsensemediated mRNA decay (40) . Thus, our study not only highlights how nidovirus helicase activity depends on the extensive relay of interactions between the ZBD, accessory and HEL1 domains but also provides a framework to propose and explore a role for the enzyme in the posttranscriptional quality control of nidovirus RNAs.