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nucleic acid binding domain of betacoronavirus non-structural protein 3 This model represents the nucleic acid binding (NAB) domain of non-structural protein 3 (Nsp3) from betacoronavirus including highly pathogenic human coronaviruses (CoVs) such as Severe acute respiratory syndrome-related coronavirus (SARS-CoV) and SARS-CoV2 (also called 2019 novel CoV or 2019-nCoV). The NAB domain represents a new fold, with a parallel four-strand beta-sheet holding two alpha-helices of three and four turns that are oriented antiparallel to the beta-strands. NAB is a cytoplasmic domain located between the papain-like protease (PLPro) and betacoronavirus-specific marker (betaSM) domains of CoV Nsp3. Nsp3 is a large multi-functional multi-domain protein that is an essential component of the replication/transcription complex (RTC), which carries out RNA synthesis, RNA processing, and interference with the host cell innate immune system. The NAB domain both binds ssRNA and unwinds dsDNA. It prefers to bind ssRNA containing repeats of three consecutive guanines. A group of residues that form a positively charged patch on the protein surface of SARS-CoV Nsp3 NAB serves as the binding site of nucleic acids. This site is conserved in the NAB of Nsp3 from betacoronavirus in the sarbecovirus subgenus (B lineage), but may not be conserved in the Nsp3 NAB from betacoronaviruses in other lineages.
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