SUD-N and SUD-M macrodomains of the SARS-Unique Domain (SUD) of SARS-CoV non-structural protein 3 and related macrodomains
This family includes two macrodomains referred to as the SUD-N (N-terminal subdomain) and SUD-M (middle SUD subdomain) of the SARS-unique domain (SUD) which bind G-quadruplexes (unusual nucleic-acid structures formed by consecutive guanosine nucleotides). It is found in non-structural protein 3 (Nsp3) of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and highly related coronaviruses. SUD consists of three globular domains separated by short linker peptide segments: SUD-N, SUD-M, and SUD-C. Among these, SUD-N and SUD-M are macrodomains. SUD-N (also called Mac2) is specific to the Nsp3 of SARS and betacoronaviruses of the sarbecovirus subgenera (B lineage), while SUD-M (also called Mac3) is present in most Nsp3 proteins except the Nsp3 from betacoronaviruses of the embecovirus subgenera (A lineage). SUD-C adopts a frataxin-like fold, has structural similarity to DNA-binding domains of DNA-modifying enzymes, binds single-stranded RNA, and regulates the RNA binding behavior of the SUD-M macrodomain. SARS-CoV Nsp3 contains a third macrodomain (the X-domain or Mac1) which is not included in this family. The X-domain may function as a module binding poly(ADP-ribose); however, SUD-N and SUD-M do not bind ADP-ribose, as the triple glycine sequence involved in its binding is not conserved in these.
Jiyao W et al.(2023). "The conserved domain database in 2023.",