First Insights into the Structural Features of Ebola Virus Methyltransferase Activities

Overview

Journal Nucleic Acids Res

Publisher Oxford University Press

Specialty Biochemistry

Date 2021 Jan 27

PMID 33503246

Citations 6

Authors

Coralie Valle

Baptiste Martin

Francois Ferron

Veronique Roig-Zamboni

Aline Desmyter

Francoise Debart

Jean-Jacques Vasseur

Bruno Canard

Bruno Coutard

Etienne Decroly

Affiliations

Soon will be listed here.

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.

Citing Articles

Coronavirus 2'-O-methyltransferase: A promising therapeutic target.

Schindewolf C, Menachery V Virus Res. 2023; 336:199211.

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Sutto-Ortiz P, Eleouet J, Ferron F, Decroly E Viruses. 2023; 15(2).

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Internal RNA 2'O-methylation in the HIV-1 genome counteracts ISG20 nuclease-mediated antiviral effect.

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