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

MERS-CoV nsp13 is composed of multiple functional domains (Fig 2, S1 and S2 Figs). The Nterminal CH domain has 15 conserved Cys/His residues, twelve of which participate in the coordination of three zinc ions ( Fig 3A & Fig 4A-4C ). The C-terminal helicase belongs to the SF1 helicase family and consists of two "RecA-like" domains, referred to as RecA1 and RecA2. The CH and helicase are connected via a region consisting two additional domains. A helical domain sandwiched between the CH and RecA1 domains is followed by a six-stranded antiparallel β-barrel domain. Because of the structural resemblance to the domains of Upf1 helicases, these domains were named as Stalk and 1B, respectively. We compared the crystal structure of MERS-CoV nsp13 with all structures in Protein Data Bank using Dali server. The top hits were human Upf1 helicase [24] (hUpf1 PDB code: 2GK7; Dali Z-score: 22.7) and arterivirus (EAV) helicase [25] (PDB code: 4N0N; Dali Z-score: 22.2). The structural superposition showed that while the helicase portion of these three proteins aligns well, the N-terminal CH (or ZBD) and 1B domains adopt various conformations relative to the helicase core.