PROSITE documentation PDOC51952
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: αcoronavirus, βcoronavirus, γcoronavirus, and Deltacoronavirus. The ideal hosts of αCoV and βCoV are mammals, and γCoV 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 βCoV [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 them, the Nsp12 RNA-dependent RNA polymerase, that includes an RdRp catalytic domain conserved in all RNA viruses (see <PDOC50507>), possesses some minimal activity on its own, but the addition of the Nsp7 and Nsp8 cofactors greatly stimulates polymerase activity (see <PDOC51948>). 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 α/β fold comprised of five α-helices (α1 to α5), one 3(10)-helix, and three β-strands (β1 to β3) (see <PDB:2G9T>). The central core of the ExoN/MTase coactivator domain is an antiparallel β-sheet formed by strands β1, β2, and β3. The central β-sheet is flanked on one side by helices α3 and α4, while helices α1, α2 at the N-terminus, helix α5, 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.

Last update:

December 2020 / First entry.


Technical section

PROSITE method (with tools and information) covered by this documentation:

COV_EXON_MTASE_COACT, PS51952; Coronavirus (CoV) ExoN/MTase coactivator domain profile  (MATRIX)


1AuthorsGorgulla C. Das K.M.P. Leigh K.E. Cespugli M. Fischer P.D. Wang Z.-F. Tesseyre G. Pandita S. Shnapir A. Calderaio A. Hutcheson C. Gechev M. Rose A. Lewis N. Yaffe E. Luxenburg R. Herce H.D. Durmaz V. Halazonetis T.D. Fackeldey K. Patten J.J. Chuprina A. Dziuba I. Plekhova A. Moroz Y. Radchenko D. Tarkhanova O. Yavnyuk I. Gruber C.C. Yust R. Payne D. Naeaer A.M. Namchuk M.N. Davey R.A. Wagner G. Kinney J. Arthanari H.
TitleA Multi-Pronged Approach Targeting SARS-CoV-2 Proteins Using Ultra-Large Virtual Screening.
SourceChemRxiv 0:0-0(2020).
PubMed ID33200116

2AuthorsBouvet M. Lugari A. Posthuma C.C. Zevenhoven J.C. Bernard S. Betzi S. Imbert I. Canard B. Guillemot J.-C. Lecine P. Pfefferle S. Drosten C. Snijder E.J. Decroly E. Morelli X.
TitleCoronavirus Nsp10, a critical co-factor for activation of multiple replicative enzymes.
SourceJ. Biol. Chem. 289:25783-25796(2014).
PubMed ID25074927

3AuthorsSu D. Lou Z. Sun F. Zhai Y. Yang H. Zhang R. Joachimiak A. Zhang X.C. Bartlam M. Rao Z.
TitleDodecamer structure of severe acute respiratory syndrome coronavirus nonstructural protein nsp10.
SourceJ. Virol. 80:7902-7908(2006).
PubMed ID16873247

4AuthorsMa Y. Wu L. Shaw N. Gao Y. Wang J. Sun Y. Lou Z. Yan L. Zhang R. Rao Z.
TitleStructural basis and functional analysis of the SARS coronavirus nsp14-nsp10 complex.
SourceProc. Natl. Acad. Sci. U. S. A. 112:9436-9441(2015).
PubMed ID26159422

5AuthorsFerron F. Subissi L. Silveira De Morais A.T. Le N.T.T. Sevajol M. Gluais L. Decroly E. Vonrhein C. Bricogne G. Canard B. Imbert I.
TitleStructural and molecular basis of mismatch correction and ribavirin excision from coronavirus RNA.
SourceProc. Natl. Acad. Sci. U. S. A. 115:E162-E171(2018).
PubMed ID29279395

6AuthorsViswanathan 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.
TitleStructural basis of RNA cap modification by SARS-CoV-2.
SourceNat. Commun. 11:3718-3718(2020).
PubMed ID32709886

7AuthorsRogstam A. Nyblom M. Christensen S. Sele C. Talibov V.O. Lindvall T. Rasmussen A.A. Andre I. Fisher Z. Knecht W. Kozielski F.
TitleCrystal Structure of Non-Structural Protein 10 from Severe Acute Respiratory Syndrome Coronavirus-2.
SourceInt. J. Mol. Sci. 21:0-0(2020).
PubMed ID33036230


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