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

Our structure further revealed that the N-terminal ZBD (Figure 2 ; yellow) has a compact fold containing three structural zinc atoms. Based on secondary structure analysis with DIAL (49), we could partition ZBD into three elements (Figure 4 ). Two adjacent and structurally different zinc fingers, an N-terminal RING-like module (residues 1-40, pink) and a treble-clef zinc finger (residues 41-65, red) constitute the main body of ZBD. The third element is a C-terminal linker region (Linker1) that includes the long loop L7, which crosses the entire domain, and helix a4 (residues 66-82, yellow), which connects the two zinc fingers with domain 1B ( Figure 4A ). This classification is further supported by the observation that the connecting residues between the RING module and treble-clef zinc finger are disordered Structure of (B) free and (C) nucleic acid-bound nsp10Á. Also the F o ÀF c differential electron density map of the bound single-stranded part of a partially double-stranded DNA substrate at 2.5 s is presented. The putative ATP binding site is shown as a brown oval. (Supplementary Figure S2 and Figure 4D ). Only 12 out of the 13 Cys/His residues are involved in zinc binding, rather than all 13 residues as proposed previously [(36); Figure 4B and C]. Not involved is His34, which is not conserved in other arteri-and coronaviruses (Supplementary Figure S3B) .