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

Substrate binding by nsp10 is accompanied by structural changes in domain 1B and the treble-clef zinc finger, which may be recognized by yet-to-be identified interaction partners modulating nsp10 function. The treble-clef finger is fairly distant from the bound substrate, suggesting long-distance signal transduction within nsp10, possibly involving helix a4, which interacts with 1A, 1B and nucleic acid and is directly connected to the treble-clef zinc finger. The flexibility of the hinge region connecting the treble-clef zinc finger and helix a4 is likely compromised by the previously described S59P and S59G/P60G mutations that, importantly, were found to impair viral sg mRNA synthesis but not genome replication (36) . Consequently, the described inter-domain communication channel may be used by nsp10 and its partners for switching from a role in genome replication to directing viral transcription, a hypothesis that will be the subject of future studies.