{PDOC51952} {PS51952; COV_EXON_MTASE_COACT} {BEGIN} *********************************************************** * Coronavirus (CoV) ExoN/MTase coactivator domain profile * *********************************************************** 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: Alphacoronavirus, Betacoronavirus, Gammacoronavirus, and Deltacoronavirus. The ideal hosts of AlphaCoV and BetaCoV are mammals, and GammaCoV primarily infects birds, while DeltaCoV has been identified in both mammals and birds. SARS, SARS-CoV-2, BatCoV RaTG13 and Bat-SARS-like coronavirus (BATSL-CoVZXC21 and BAT-SL-CoVZC45) belong to the Sarbecovirus subgenus of BetaCoV [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 ) and of one or two papain-like proteases (PLpro) (see ) found in Nsp3 into non-structural proteins (Nsps) to form the replication/ transcription complex (RTC). Among them, the Nsp12 RNA-dependent RNA polymerase, that includes an RdRp catalytic domain conserved in all RNA viruses (see ), possesses some minimal activity on its own, but the addition of the Nsp7 and Nsp8 cofactors greatly stimulates polymerase activity (see ). The Nsp12-Nsp7-Nsp8 subcomplex is thus defined as the minimal core component for mediating CoV RNA synthesis with additional Nsps playing roles in RNA modification. Nsp10, a critical cofactor for activation of multiple replicative enzymes, is a small protein of ca. 140 amino acid residues that exists exclusively in viruses and not in prokaryotes or eukaryotes. Nsp10 is known to interact with both Nsp14 and Nsp16, acting as a scaffolding protein and stimulating their respective 3'-5' exoribonuclease (ExoN) and 2'-O-methyltransferase (2'-O-MTase) activities [1,2,3,4,5,6,7]. The ExoN/MTase coactivator domain has a mixed alpha/beta fold comprised of five alpha-helices (alpha1 to alpha5), one 3(10)-helix, and three beta-strands (beta1 to beta3) (see ). The central core of the ExoN/MTase coactivator domain is an antiparallel beta-sheet formed by strands beta1, beta2, and beta3. The central beta-sheet is flanked on one side by helices alpha3 and alpha4, while helices alpha1, alpha2 at the N-terminus, helix alpha5, and the extended C-terminal coil shy away from the central core. The ExoN/MTase coactivator domain is cysteine-rich, featuring two zinc fingers with C-x(2)-C-x(5)-H-x(6)-C and C-x(2)-C-x(7)-C-x-C motifs. 12 identical subunits assemble to form a unique spherical dodecameric architecture, which is proposed to be a functional form of the ExoN/MTase coactivator domain [3,4,5,6,7]. The profile we developed covers the entire CoV ExoN/MTase coactivator domain. -Sequences known to belong to this class detected by the profile: ALL. -Other sequence(s) detected in Swiss-Prot: NONE. -Last update: December 2020 / First entry. 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PubMed=29279395; DOI=10.1073/pnas.1718806115 [ 6] Viswanathan T., Arya S., Chan S.-H., Qi S., Dai N., Misra A., Park J.-G., Oladunni F., Kovalskyy D., Hromas R.A., Martinez-Sobrido L., Gupta Y.K. "Structural basis of RNA cap modification by SARS-CoV-2." Nat. Commun. 11:3718-3718(2020). PubMed=32709886; DOI=10.1038/s41467-020-17496-8 [ 7] Rogstam A., Nyblom M., Christensen S., Sele C., Talibov V.O., Lindvall T., Rasmussen A.A., Andre I., Fisher Z., Knecht W., Kozielski F. "Crystal Structure of Non-Structural Protein 10 from Severe Acute Respiratory Syndrome Coronavirus-2." Int. J. Mol. Sci. 21:0-0(2020). PubMed=33036230; DOI=10.3390/ijms21197375 [E1] https://viralzone.expasy.org/30?outline=all_by_species -------------------------------------------------------------------------------- PROSITE is copyrighted by the SIB Swiss Institute of Bioinformatics and distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND 4.0) License, see https://prosite.expasy.org/prosite_license.html -------------------------------------------------------------------------------- {END}