| Primary Identifier | IPR043478 | Type | Homologous_superfamily |
| Short Name | NSP3_SUD-N_sf_bCoV |
| description | This superfamily represents the N-terminal region of the SUD domain (SUD-N or Mac2) found in non-structural protein NSP3, the product of ORF1a in group 2 (beta) coronaviruses. It is found in human SARS-CoV and SARS-CoV-2 polyprotein 1a and 1ab, and in related coronavirus polyproteins [].Non-structural protein Nsp3 contains at least seven different functional modules within its 1922-amino-acid polypeptide chain. One of these is the so-called SARS (severe acute respiratory syndrome)-unique domain (SUD), a stretch of about 338 residues that is completely absent from any other coronavirus. The SUD domain may be responsible for the high pathogenicity of the SARS coronavirus, compared to other viruses of this family [, ]. Later, the NSP3 of MHV was shown by X-ray crystallography to contain a SUD-C-like fold, so it is no longer appropriate to call this domain "SARS-unique". This region has been renamed into "Domain Preceding Ubl2 and PL2pro"(DPUP) []. NSP3 has been shown to bind to viral RNA, nucleocapsid protein, as well as other viral proteins, and participates in polyprotein processing. It is a multifunctional protein comprising up to 16 different domains and regions []. SUD(core) exhibits a two-domain architecture. The N-terminal subdomain (SUD-N) and the C-terminal subdomain of SUDcore, also named middle SUD subdomain, or SUD-M [, ]. SUD-N has been shown to be dispensable for the SARS-CoV replication/transcription complex within the context of a SARS-CoV replicon []. 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. The SUD-N domain is a related macrodomain which also binds G-quadruplexes []. While SUD-N is specific to the NSP3 of SARS and betacoronaviruses of the sarbecovirus subgenera (B lineage), SUD-M is present in most NSP3 proteins except the NSP3 from betacoronaviruses of the embecovirus subgenera (A lineage). SUD-M, despite its name, is not specific to SARS. 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). 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 []. |
