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

We compared the isolated CH/ZBD of MERS-CoV nsp13, EAV nsp10 and Upf1 (Table 2) , and found that the CH of MERS-CoV nsp13 is structurally more related to the CH of Upf1 than to the ZBD of EAV nsp10. Superimposition of yeast Upf1 CH (scUpf1 PDB code: 2XZL) and MERS-CoV nsp13 CH aligned 102 Cα atoms with the Dali Z-score of 10.2 and rmsd of 2.2Å. Superimposition of EAV nsp10 CH (PDB code: 4N0N) and MERS-CoV nsp13 CH aligned 59 Cα atoms with the Dali Z-score of 4.4 and rmsd of 3.4Å. Additionally, while the positions of three zincs of MERS-CoV nsp13 CH domain and Upf1 CH domain are nearly identical, Zn3 of EAV nsp10 ZBD is located much closer to Zn1 and Zn2. Particularly, the distance from Zn3 to Zn2 is~6.4Å shorter in EAV nsp10 than the corresponding distance in MERS nsp13 (Fig 4B) . However, the interaction between the CH domain and the helicase region is significantly different between nidovirus helicases and Upf1, and similar between MERS-CoV nsp13 and EAV nsp10. The MERS-CoV nsp13 CH domain is tightly attached to the Stalk domain ( Fig 5A) . Helices α2-α4 form a three-helical bundle. The buried area between CH and Stalk is 1670Å 2 . Similarly, the EAV nsp10 ZBD domain is connected to the stalk domain, which is significantly smaller than CH of MERS-CoV nsp13 (Fig 5B) . The buried area between ZBD and Stalk is 634.7 Å 2 . By contrast, the CH of Upf1 helicase is linked to the helicase portion through a long and flexible loop (often invisible in the electron density maps), allowing large movement of the CH domain (Fig 5C and 5D ) [26] .