First insights into the structural features of Ebola virus methyltransferase activities.
Journal
Nucleic acids research
ISSN: 1362-4962
Titre abrégé: Nucleic Acids Res
Pays: England
ID NLM: 0411011
Informations de publication
Date de publication:
22 02 2021
22 02 2021
Historique:
accepted:
22
12
2020
revised:
18
12
2020
received:
29
08
2020
pubmed:
28
1
2021
medline:
4
3
2021
entrez:
27
1
2021
Statut:
ppublish
Résumé
The Ebola virus is a deadly human pathogen responsible for several outbreaks in Africa. Its genome encodes the 'large' L protein, an essential enzyme that has polymerase, capping and methyltransferase activities. The methyltransferase activity leads to RNA co-transcriptional modifications at the N7 position of the cap structure and at the 2'-O position of the first transcribed nucleotide. Unlike other Mononegavirales viruses, the Ebola virus methyltransferase also catalyses 2'-O-methylation of adenosines located within the RNA sequences. Herein, we report the crystal structure at 1.8 Å resolution of the Ebola virus methyltransferase domain bound to a fragment of a camelid single-chain antibody. We identified structural determinants and key amino acids specifically involved in the internal adenosine-2'-O-methylation from cap-related methylations. These results provide the first high resolution structure of an ebolavirus L protein domain, and the framework to investigate the effects of epitranscriptomic modifications and to design possible antiviral drugs against the Filoviridae family.
Identifiants
pubmed: 33503246
pii: 6121458
doi: 10.1093/nar/gkaa1276
pmc: PMC7897494
doi:
Substances chimiques
Single-Domain Antibodies
0
Viral Proteins
0
Methyltransferases
EC 2.1.1.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1737-1748Informations de copyright
© The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research.
Références
Nucleic Acids Res. 2016 Jul 8;44(W1):W351-5
pubmed: 27131377
J Virol. 2008 Dec;82(24):12280-90
pubmed: 18829753
Nucleic Acids Res. 2016 Sep 19;44(16):e135
pubmed: 27302133
PLoS Negl Trop Dis. 2017 Oct 9;11(10):e0005996
pubmed: 28991917
RNA. 2012 Apr;18(4):856-68
pubmed: 22334760
Cell. 2019 Sep 19;179(1):193-204.e14
pubmed: 31495574
Trends Biochem Sci. 2002 May;27(5):222-4
pubmed: 12076527
J Virol. 2009 Nov;83(21):11043-50
pubmed: 19710136
Nat Methods. 2017 Jul;14(7):695-698
pubmed: 28504680
J Virol. 2020 Jun 1;94(12):
pubmed: 32269120
Proc Natl Acad Sci U S A. 2010 Nov 16;107(46):20075-80
pubmed: 21041632
Cell. 2015 Jul 16;162(2):314-327
pubmed: 26144317
Acta Crystallogr D Biol Crystallogr. 2010 Apr;66(Pt 4):470-8
pubmed: 20383000
Curr Opin Virol. 2017 Feb;22:51-58
pubmed: 28012412
Protein Sci. 2018 Jan;27(1):293-315
pubmed: 29067766
Acta Crystallogr D Biol Crystallogr. 2004 Dec;60(Pt 12 Pt 1):2256-68
pubmed: 15572779
Proc Natl Acad Sci U S A. 2020 Jan 28;117(4):2099-2107
pubmed: 31953264
Nucleic Acids Res. 2018 Sep 6;46(15):7902-7912
pubmed: 30192980
J Comput Chem. 2004 Oct;25(13):1605-12
pubmed: 15264254
Cell. 1976 Dec;9(4 PT 2):645-53
pubmed: 1017010
Proc Natl Acad Sci U S A. 2016 Jan 19;113(3):596-601
pubmed: 26733676
Protein Eng. 2002 Feb;15(2):101-8
pubmed: 11917146
PLoS Pathog. 2012;8(4):e1002642
pubmed: 22496660
Proc Natl Acad Sci U S A. 2020 Mar 3;117(9):4931-4941
pubmed: 32075920
Biochemistry. 2019 Jan 22;58(3):166-170
pubmed: 30406995
Immunity. 2015 Jul 21;43(1):41-51
pubmed: 26187414
J Virol. 2017 Feb 14;91(5):
pubmed: 28031359
Virus Res. 1993 Sep;29(3):215-40
pubmed: 8237108
Proc Natl Acad Sci U S A. 2013 Apr 9;110(15):E1371-9
pubmed: 23530214
Nat Commun. 2015 Nov 09;6:8749
pubmed: 26549102
Nucleic Acids Res. 2016 Jan 8;44(1):330-41
pubmed: 26602696
Drug Discov Today. 2020 Jun;25(6):1026-1033
pubmed: 32272194
Proc Natl Acad Sci U S A. 2001 Aug 28;98(18):10037-41
pubmed: 11517324
Arch Virol. 1993;133(3-4):423-36
pubmed: 8257297
Acta Crystallogr D Biol Crystallogr. 2006 Sep;62(Pt 9):1002-11
pubmed: 16929101
Science. 1988 May 20;240(4855):1038-41
pubmed: 3285470
Acta Crystallogr D Biol Crystallogr. 2004 Dec;60(Pt 12 Pt 1):2210-21
pubmed: 15572774
EMBO J. 1998 Jul 1;17(13):3512-20
pubmed: 9649422
J Gen Virol. 1990 May;71 ( Pt 5):1153-62
pubmed: 2161049
Cell. 2020 Apr 2;181(1):6
pubmed: 32243796
Acta Crystallogr D Biol Crystallogr. 2004 Dec;60(Pt 12 Pt 1):2126-32
pubmed: 15572765
Acta Crystallogr D Biol Crystallogr. 2011 Apr;67(Pt 4):293-302
pubmed: 21460447
Acta Crystallogr D Biol Crystallogr. 2013 Jul;69(Pt 7):1204-14
pubmed: 23793146
Nat Rev Genet. 2017 May;18(5):275-291
pubmed: 28216634
J Virol. 2009 Feb;83(4):1930-40
pubmed: 19073725
Nature. 2019 Jan;565(7740):500-504
pubmed: 30626973
Nature. 2020 Jan;577(7789):275-279
pubmed: 31698413
J Appl Crystallogr. 2007 Aug 1;40(Pt 4):658-674
pubmed: 19461840
Mol Cell. 2007 Jan 12;25(1):85-97
pubmed: 17218273
Org Lett. 2010 May 21;12(10):2190-3
pubmed: 20420425
Nucleic Acids Res. 2014 Jul;42(Web Server issue):W320-4
pubmed: 24753421