Cys/His rich zinc-binding domain (CH/ZBD) of coronavirus SARS NSP13 helicase and related proteins
Helicases catalyze NTP-dependent unwinding of nucleic acid duplexes into single strands and are classified based on the arrangement of conserved motifs into six superfamilies. This coronavirus family includes Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) non-structural protein 13 (SARS-Nsp13) and belongs to helicase superfamily 1 (SF1) and to a family of nindoviral replication helicases. SARS-Nsp13 has an N-terminal CH/ZBD, a stalk domain, a 1B regulatory domain, and SF1 helicase core. The CH/ZBD has 3 zinc-finger (ZnF1-3) motifs. SARS-Nsp13 is a component of the viral RNA synthesis replication and transcription complex (RTC). The SARS-Nsp13 CH/ZBD is indispensable for helicase activity and interacts with SARS-Nsp12, the RNA-dependent RNA polymerase (RdRp). Structural studies of a stable SARS-CoV-2 RTC which included two molecules of Nsp13, the RdRp holoenzyme (Nsp7, two molecules of Nsp8, Nsp12), and an RNA template product, show that one Nsp13 CH/ZBD domain interacts with Nsp12, and both Nsp13-CH/ZBD domains interact with the Nsp8. This stable SARS-CoV-2 RTC suggests that the Nsp13 helicase may drive RTC backtracking, affecting proofreading and template switching.
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