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

Autor: Skvara P; Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, V.v.i, Flemingovo nám. 2, 16610, Prague 6, Czech Republic., Chalupska D; Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, V.v.i, Flemingovo nám. 2, 16610, Prague 6, Czech Republic., Klima M; Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, V.v.i, Flemingovo nám. 2, 16610, Prague 6, Czech Republic., Kozic J; Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, V.v.i, Flemingovo nám. 2, 16610, Prague 6, Czech Republic., Silhan J; Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, V.v.i, Flemingovo nám. 2, 16610, Prague 6, Czech Republic., Boura E; Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, V.v.i, Flemingovo nám. 2, 16610, Prague 6, Czech Republic. Electronic address: boura@uochb.cas.cz.
Jazyk: angličtina
Zdroj: Antiviral research [Antiviral Res] 2023 Aug; Vol. 216, pp. 105663. Date of Electronic Publication: 2023 Jul 07.
DOI: 10.1016/j.antiviral.2023.105663
Abstrakt: 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.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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