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

The N-terminal RING-like module has a notable binuclear structure with a cross-brace topology involving 6 Cys and 2 His residues that coordinate two zinc ions ( Figure 4A) . A three-stranded antiparallel b-sheet (b1-b3) sits in the centre and packs against helix a1 following b2 ( Figure 4B ). The first zinc ion (Zn1) is coordinated by four cysteine residues (Cys4, Cys7, Cys22 and Cys25) within a treble-clef zinc finger-like motif. Residues Cys4 and Cys7 are provided by the zinc knuckle within loop L1, whereas Cys22 is positioned at the C-terminus of b2 and Cys25 comes from the N-terminus of helix a1. The second zinc ion (Zn2) is coordinated by residues Cys17, Cys33, His29 and His32, which are arranged in an abb zinc finger-like motif. The second pair of the zinc-coordinating residues of both zinc-binding motifs of the RING module may include both His and Cys residues in other arteri-and coronaviruses. Overall, the RING module of these viruses can be described by a characteristic conserved Cys2 A -Cys B -Cys[His/Cys] A -[His/Cys]3 B pattern (where applicable, A and B refer to residues chelating the first and second zinc ion, respectively; brackets indicate positions at which His and Cys can alternate).