|PROSITE documentation PDOC51940|
Coronaviruses (CoVs) are enveloped positive-strand RNA viruses that infect many species, including humans, other mammals, and birds. After infection, the host may develop respiratory, bowel, liver, and neurological diseases. Coronaviruses are divided into four genera: αcoronavirus, βcoronavirus, γcoronavirus, and Deltacoronavirus. SARS, SARS-CoV-2, BatCoV RaTG13 and Bat-SARS-like coronavirus (BATSL-CoVZXC21 and BAT-SL-CoVZC45) belong to the Sarbecovirus subgenus of βcoronavirus [E1].
The CoV replicase gene encodes two overlapping polyproteins, termed pp1a and pp1ab, which mediate viral replication and transcription. The polypeptides pp1a and pp1ab are processed by the action of a main protease (Nsp5) (see <PDOC51442>) and of one or two papain-like proteases (PLpro) (see <PDOC51124>) found in Nsp3 into non-structural proteins (Nsps) to form the replication/ transcription complex (RTC). Among these, Nsp3 is a glycosylated, multidomain, integral membrane protein. Nsp3 plays many roles in the viral life cycle. It can act as a scaffold protein to interact with itself and to bind other viral Nsps or host proteins. In particular, Nsp3 is essential for RTC formation. Nsp3 comprises various domains, the organization of which differs between CoV genera, due to duplication or absence of some domains . Among other domains, Sarbecovirus Nsp3 contains three sequentially arranged Macro domains: the X domain (see <PDOC51154>) and domains Nsp3c-N (or SUD-N) as well as Nsp3c-M (or SUD-M) within the Nsp3C or SUD (SARS-unique domain) region. Called "X-domains", single Macro domains are also found in αviruses, in hepatitis E virus, and in rubella virus, in addition to coronaviruses. The Nsp3c-M domain is not limited to Sarbecoviruses but is also found in other βcoronaviruses like MERS-CoV (Merbecovirus subgenus). While the Nsp3c-N and X domains are dispensable, the Nsp3c-M domain is crucial for viral genome replication/transcription [2,3,,4,5].
Nsp3c-N and Nsp3c-M each display a typical α/β/α Macro domain fold (see <PDB:2W2G>), in spite of the complete absence of sequence similarities. The central β sheet with six β strands in the order β1-β6-β5-β2-β4-β3 is flanked by two (or three) helices on either side. Only the last strand, β3, is antiparallel to the other strands. Currently, most known functions of Nsp3c-N/M are connected with RNA binding. All the residues important for binding ADP-ribose and for de-MARylation/de-PARylation activity are not conserved in Nsp3c-N/M; therefore Nsp3c-N/M cannot bind ADP-ribose. Both Nsp3c-N and Nsp3c-M domains bind unusual nucleic-acid structures formed by consecutives guanosine nucleotides, where four strands of nucleic acid are forming a superhelix (so-celled G-quadruplexes) [1,2,3,4,5].
The profiles we developed cover the entire Nsp3c-N and Nsp3c-M domains.Last update:
September 2020 / First entry.
PROSITE methods (with tools and information) covered by this documentation:
|1||Authors||Tan J. Vonrhein C. Smart O.S. Bricogne G. Bollati M. Kusov Y. Hansen G. Mesters J.R. Schmidt C.L. Hilgenfeld R.|
|Title||The SARS-unique domain (SUD) of SARS coronavirus contains two macrodomains that bind G-quadruplexes.|
|Source||PLoS Pathog. 5:E1000428-E1000428(2009).|
|2||Authors||Chatterjee A. Johnson M.A. Serrano P. Pedrini B. Joseph J.S. Neuman B.W. Saikatendu K. Buchmeier M.J. Kuhn P. Wuethrich K.|
|Title||Nuclear magnetic resonance structure shows that the severe acute respiratory syndrome coronavirus-unique domain contains a macrodomain fold.|
|Source||J. Virol. 83:1823-1836(2009).|
|3||Authors||Johnson M.A. Chatterjee A. Neuman B.W. Wuethrich K.|
|Title||SARS coronavirus unique domain: three-domain molecular architecture in solution and RNA binding.|
|Source||J. Mol. Biol. 400:724-742(2010).|
|4||Authors||Kusov Y. Tan J. Alvarez E. Enjuanes L. Hilgenfeld R.|
|Title||A G-quadruplex-binding macrodomain within the 'SARS-unique domain' is essential for the activity of the SARS-coronavirus replication-transcription complex.|
|5||Authors||Lei J. Kusov Y. Hilgenfeld R.|
|Title||Nsp3 of coronaviruses: Structures and functions of a large multi-domain protein.|
|Source||Antiviral. Res. 149:58-74(2018).|