Structural basis for RNA-cap recognition and methylation by the mpox methyltransferase VP39

0574061 - ÚOCHB 2024 RIV NL eng J - Journal Article
Škvára, Petr - Chalupská, Dominika - Klíma, Martin - Kozic, Ján - Šilhán, Jan - Bouřa, Evžen
Structural basis for RNA-cap recognition and methylation by the mpox methyltransferase VP39.
Antiviral Research. Roč. 216, August (2023), č. článku 105663. ISSN 0166-3542. E-ISSN 1872-9096
R&D Projects: GA MŠMT(CZ) LX22NPO5103
Institutional support: RVO:61388963
Keywords : messenger-RNA * virus methyltransferase
OECD category: Virology
Impact factor: 7.6, year: 2022
Method of publishing: Open access
https://doi.org/10.1016/j.antiviral.2023.105663

Mpox is a zoonotic disease caused by the mpox virus (MPXV), which has gained attention due to its rapid and widespread transmission, with reports from more than 100 countries. The virus belongs to the Orthopoxvirus genus, which also includes variola virus and vaccinia virus. In poxviruses, the RNA cap is crucial for the translation and stability of viral mRNAs and also for immune evasion. This study presents the crystal structure of the mpox 2′-O-methyltransfarase VP39 in complex with a short cap-0 RNA. The RNA substrate binds to the protein without causing any significant changes to its overall fold and is held in place by a combination of electrostatic interactions, π-π stacking and hydrogen bonding. The structure also explains the mpox VP39 preference for a guanine base at the first position, it reveals that guanine forms a hydrogen bond that an adenine would not be able to form.
Permanent Link: https://hdl.handle.net/11104/0344428


Research data: PDB