Home  |  Contact
PROSITE documentation PDOC51955

Nidovirus 2'-O-methyltransferase (2'-O-MTase) domain profile





Description

Positive-stranded RNA (+RNA) viruses that belong to the order Nidovirales infect a wide range of vertebrates (families Arteriviridae and Coronaviridae) or invertebrates (Mesoniviridae and Roniviridae). Examples of nidoviruses with high economic and societal impact are the arterivirus porcine reproductive and respiratory syndrome virus (PRRSV) and the zoonotic coronaviruses (CoVs) causing severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS) and Covid-19 (SARS-CoV-2) in humans.

In all nidoviruses, at least two-thirds of the capacity of the polycistronic genome is occupied by the two large open reading frames (ORFs; 1a and 1b) that together constitute the replicase gene. The two polyproteins produced, pp1a (ORF1a-encoded) and pp1ab (ORF1a/ORF1b-encoded), are processed to a dozen or more proteins by the virus’ main protease (3CLpro, encoded in ORF1a) (see <PDOC51442>) with possible involvement of other protease(s). The 3'-terminal domain of the most conserved ORF1b in three of the four families of the order Nidovirales (except for the family Arteriviridae) encodes a 2'-O-methyltransferase (2'-O-MTase), known as non structural protein (Nsp) 16 in the family Coronaviridae and implicated in methylation of the 5' cap structure of nidoviral mRNAs. Assembly of a cap1 structure at the 5' end of viral mRNA assists in translation and evading host defense. The cap structure consists of a 7-methylguanosine (m7G) linked to the first nucleotide of the RNA transcript through a 5'-5' triphosphate bridge. Formation of this cap in CoV requires four sequential reactions. First, Nsp13 RNA triphosphatase (RTPase) hydrolyzes nascent RNA to yield pp-RNA. Then an unknown guanylyl-transferase (GTase) hydrolyzes GTP, transfers the product GMP to pp-RNA, and creates Gppp-RNA. Then Nsp14 methylates the 5' guanine of the Gppp-RNA at the N7 position (see <PDOC51954>), followed by methylation of the ribose of the first nucleotide at the 2'-O-position by Nsp16. The CoV Nsp16 methyltransferase forms an obligatory complex with Nsp10 (see<PDOC51952>) to efficiently convert client mRNA species from the cap-0 ((me7)G(0)pppA(1)) to the cap-1 form ((me7)G(0)pppA(1m)) by methylating the ribose 2'-O of the first nucleotide (usually adenosine in CoVs) of the nascent mRNA using S-adenosyl methionine (SAM) as the methyl donor [1,2,3,4].

The nidovirus 2'-O-MTase domain exhibits the characteristic fold of the class I MTase family, comprising a β-sheet flanked by α helices and loops (see <PDB:3R24>). The β-sheet MTase fold has been described as having a secondary structure topology defining two binding domains, one for SAM and the other for the methyl acceptor substrate. The nidovirus 2'-O-MTase domain harbors a catalytic K-D-K-E tetrad that is conserved among 2'-O-MTases [5,6,7].

The profile we developed covers the entire nidovirus 2'-O-MTase domain.

Last update:

January 2021 / First entry.

-------------------------------------------------------------------------------

Technical section

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

NIV_2_O_MTASE, PS51955; Nidovirus 2'-O-methyltransferase (2'-O-MTase) domain profile  (MATRIX)


References

1AuthorsNga P.T. Parquet Mdel C. Lauber C. Parida M. Nabeshima T. Yu F. Thuy N.T. Inoue S. Ito T. Okamoto K. Ichinose A. Snijder E.J. Morita K. Gorbalenya A.E.
TitleDiscovery of the first insect nidovirus, a missing evolutionary link in the emergence of the largest RNA virus genomes.
SourcePLoS Pathog. 7:E1002215-E1002215(2011).
PubMed ID21931546
DOI10.1371/journal.ppat.1002215

2AuthorsLehmann K.C. Hooghiemstra L. Gulyaeva A. Samborskiy D.V. Zevenhoven-Dobbe J.C. Snijder E.J. Gorbalenya A.E. Posthuma C.C.
TitleArterivirus nsp12 versus the coronavirus nsp16 2'-O-methyltransferase: comparison of the C-terminal cleavage products of two nidovirus pp1ab polyproteins.
SourceJ. Gen. Virol. 96:2643-2655(2015).
PubMed ID26041874
DOI10.1099/vir.0.000209

3AuthorsZeng C. Wu A. Wang Y. Xu S. Tang Y. Jin X. Wang S. Qin L. Sun Y. Fan C. Snijder E.J. Neuman B.W. Chen Y. Ahola T. Guo D.
TitleIdentification and Characterization of a Ribose 2'-O-Methyltransferase Encoded by the Ronivirus Branch of Nidovirales.
SourceJ. Virol. 90:6675-6685(2016).
PubMed ID27170751
DOI10.1128/JVI.00658-16

4AuthorsSnijder E.J. Decroly E. Ziebuhr J.
TitleThe Nonstructural Proteins Directing Coronavirus RNA Synthesis and Processing.
SourceAdv. Virus. Res. 96:59-126(2016).
PubMed ID27712628
DOI10.1016/bs.aivir.2016.08.008

5AuthorsChen Y. Su C. Ke M. Jin X. Xu L. Zhang Z. Wu A. Sun Y. Yang Z. Tien P. Ahola T. Liang Y. Liu X. Guo D.
TitleBiochemical and structural insights into the mechanisms of SARS coronavirus RNA ribose 2'-O-methylation by nsp16/nsp10 protein complex.
SourcePLoS Pathog. 7:E1002294-E1002294(2011).
PubMed ID22022266
DOI10.1371/journal.ppat.1002294

6AuthorsDecroly E. Debarnot C. Ferron F. Bouvet M. Coutard B. Imbert I. Gluais L. Papageorgiou N. Sharff A. Bricogne G. Ortiz-Lombardia M. Lescar J. Canard B.
TitleCrystal structure and functional analysis of the SARS-coronavirus RNA cap 2'-O-methyltransferase nsp10/nsp16 complex.
SourcePLoS Pathog. 7:E1002059-E1002059(2011).
PubMed ID21637813
DOI10.1371/journal.ppat.1002059

7AuthorsViswanathan 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
DOI10.1038/s41467-020-17496-8



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 prosite_license.html.

Miscellaneous

View entry in original PROSITE document format
View entry in raw text format (no links)