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First insights into the structural features of Ebola virus methyltransferase activities
- Source :
- Nucleic Acids Research, Nucleic Acids Research, 2021, 49 (3), pp.1737-1748. ⟨10.1093/nar/gkaa1276⟩, Nucleic Acids Research, Oxford University Press, 2021, 49 (3), pp.1737-1748. ⟨10.1093/nar/gkaa1276⟩
- Publication Year :
- 2021
- Publisher :
- HAL CCSD, 2021.
-
Abstract
- 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.
- Subjects :
- Models, Molecular
Protein Conformation, alpha-Helical
[SDV.BBM.BS] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM]
AcademicSubjects/SCI00010
viruses
Protein domain
Filoviridae
Crystallography, X-Ray
medicine.disease_cause
Genome
Viral Proteins
03 medical and health sciences
Structural Biology
Catalytic Domain
Genetics
medicine
Mononegavirales
Polymerase
030304 developmental biology
[SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology
Ebolavirus
0303 health sciences
Ebola virus
biology
[SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM]
030302 biochemistry & molecular biology
RNA
Methyltransferases
Single-Domain Antibodies
biology.organism_classification
3. Good health
Mutation
[SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology
biology.protein
Subjects
Details
- Language :
- English
- ISSN :
- 03051048 and 13624962
- Database :
- OpenAIRE
- Journal :
- Nucleic Acids Research, Nucleic Acids Research, 2021, 49 (3), pp.1737-1748. ⟨10.1093/nar/gkaa1276⟩, Nucleic Acids Research, Oxford University Press, 2021, 49 (3), pp.1737-1748. ⟨10.1093/nar/gkaa1276⟩
- Accession number :
- edsair.doi.dedup.....f533a9ac97d6f0a99553d8c5faf4ee22