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 C-terminal zinc finger of ZBD adopts a treble-clef fold distinct from that of the RING module (see above; Figure 4C ). Two one-turn helices a2 and a3 are stabilized by a zinc atom (Zn3) that is chelated by residues Cys42 and His44 of a Zn-knuckle within loop L5, while Cys53 and Cys56 originate from L6 and a3, respectively. An extensive array of hydrogen bonds is observed between the main chains of residues in loop L7 and Thr54 in a3 ( Figure 4D ). These multiple hydrogen-bonding interactions play a major role in the formation of a compact zinc finger. Arteri-and coronaviruses appear to tolerate replacements (Cys for His, or vice versa) at the second and fourth residues of this finger (36, 37) , which can be described by the characteristic, conserved C[H/C]C[C/H] pattern. Finally, Linker 1 includes only one structured element (a4), but it plays a central role in the interaction between the main body of ZBD and HEL1, as detailed below.