First insights into the structural features of Ebola virus methyltransferase activities. Issue 3 (27th January 2021)

• Record Type: Journal Article
• Authors: Valle, Coralie; Martin, Baptiste; Ferron, François; Roig-Zamboni, Véronique; Desmyter, Aline; Debart, Françoise; Vasseur, Jean-Jacques; Canard, Bruno; Coutard, Bruno; Decroly, Etienne
• Is Part Of: Nucleic acids research. Volume 49:Issue 3(2021)
• Page Start: 1737
• Page End: 1748
• Publication Date: 2021-01-27
• Subjects: Nucleic acids -- Periodicals; Molecular biology -- Periodicals; 572.805
• DOI: 10.1093/nar/gkaa1276
• Languages: English
• ISSNs: 0305-1048

Abstract

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.