Crystal structure of Middle East respiratory syndrome coronavirus helicase

Hao, Wei; Wojdyla, Justyna Aleksandra; Zhao, Rong; Han, Ruiyun; Das, Rajat; Zlatev, Ivan; Manoharan, Muthiah; Wang, Meitian; Cui, Sheng

In summary, our current study presents the first structural insight into the multiple functionality of the CoV nsp13. Our analyses demonstrate that while the domain organization of MERS-CoV nsp13 and EAV nsp10 is conserved, the structures of the individual domains of nsp13 are closely related to their eukaryotic equivalents in Upf1 helicase. While the interaction between the CH (or ZBD) domain and the helicase core presents the most distinctive feature differentiating nidovirus helicases from the Upf1 helicases, the high resemblance between the CH domains of MERS-CoV nsp13 and Upf1 helicases is remarkable. This structural similarity not only supports a hypothesis that nidoviruses helicase may have a Upf1-like role in posttranscriptional quality control of viral RNAs synthesis [25] , but also implies a possibility that CoV nsp13 might use its Upf1-similar CH domain to interfere with nonsense-mediated mRNA decay (NMD) pathway. It has already been shown that NMD targets viral RNAs for degradation in the early phase of infection of +RNA viruses [37] . Based on the coevolution of virus and host mechanism, the viruses also develop strategies to suppress NMD. Nevertheless, whether CoV nsp13 is involved in NMD suppression requires experimental evidence. To investigate what proteins bind nsp13 through its CH domain and how do they modulate nsp13 function is important to expand our knowledge about the evolution and function of Upf1-like helicases. Finally, our results provide novel structural information essential for structure-based drug design against CoV.