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

Sequence conservation analysis indicates that CoV nsp13 belongs to SF1 superfamily, including Rep, UvrD, PcrA, RecD, Pif1, Dda, Upf1-like helicases and many +RNA virus helicases [18, 23] . Nidovirus helicases share many structural features with the eukaryotic Upf1 helicase, a key factor in nonsense-mediated mRNA decay in cells [24, 25] . Upf1 is a multi-domain protein comprising of an N-terminal Cys-His-rich domain (CH domain) coordinating three zinc atoms, a 1B domain with the β-barrel fold and a conserved SF1 helicase core with a 1C insert in the first RecA-like domain [24, 26] . The crystal structure of nsp10 from equine arteritis virus (EAV) of Arterovirus genus is the first high-resolution structure of nidovirus helicase. EAV nsp10 has an N-terminal zinc-binding domain (ZBD) that is followed by the 1B and a SF1 helicase core, but it lacks the 1C insert. The ZBD of nsp10 coordinates two zinc ions by an N-terminal RING-like module and one zinc ion by a C-terminal treble-clef zinc finger. The 1B domain of nsp10 undergoes large conformational change upon substrate binding, and 1B together with the 1A and 2A domains of the helicase core form a channel that accommodates the single stranded nucleic acids. The CH domain of Upf1 mediates the binding with Upf2 [26] . Similarly, the ZBD of nsp10 harbors a putative protein interaction surface, of which the binding partner remains to be identified [25] . The structural resemblance between Upf1 and EAV nsp10 suggests that nidovirus helicase may be involved in the posttranscriptional quality control of the viral RNAs.