5N8X

Trigonal structure of mutant V173I of 3D polymerase from Foot-and-Mouth Disease Virus

5N8X の概要

• エントリーDOI: 10.2210/pdb5n8x/pdb
• 関連するPDBエントリー: 1U09 1WNE
• 分子名称: 3D polymerase, MANGANESE (II) ION, GLYCEROL, ... (4 entities in total)
• 機能のキーワード: 3dpolymerase, rna dependent rna polymerases, 5'-fluoracil, nucleotide analogues, viral protein
• 由来する生物種: Foot-and-mouth disease virus
• 細胞内の位置: Host cytoplasmic vesicle membrane ; Peripheral membrane protein ; Cytoplasmic side . Virion : A4H1Z0
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 54639.78

構造登録者

Ferrer-Orta, C.,Verdaguer, N. (登録日: 2017-02-24, 公開日: 2017-05-10, 最終更新日: 2024-01-17)

主引用文献

de la Higuera, I.,Ferrer-Orta, C.,de Avila, A.I.,Perales, C.,Sierra, M.,Singh, K.,Sarafianos, S.G.,Dehouck, Y.,Bastolla, U.,Verdaguer, N.,Domingo, E.
Molecular and Functional Bases of Selection against a Mutation Bias in an RNA Virus.
Genome Biol Evol, 9:1212-1228, 2017

PubMed Abstract: The selective pressures acting on viruses that replicate under enhanced mutation rates are largely unknown. Here, we describe resistance of foot-and-mouth disease virus to the mutagen 5-fluorouracil (FU) through a single polymerase substitution that prevents an excess of A to G and U to C transitions evoked by FU on the wild-type foot-and-mouth disease virus, while maintaining the same level of mutant spectrum complexity. The polymerase substitution inflicts upon the virus a fitness loss during replication in absence of FU but confers a fitness gain in presence of FU. The compensation of mutational bias was documented by in vitro nucleotide incorporation assays, and it was associated with structural modifications at the N-terminal region and motif B of the viral polymerase. Predictions of the effect of mutations that increase the frequency of G and C in the viral genome and encoded polymerase suggest multiple points in the virus life cycle where the mutational bias in favor of G and C may be detrimental. Application of predictive algorithms suggests adverse effects of the FU-directed mutational bias on protein stability. The results reinforce modulation of nucleotide incorporation as a lethal mutagenesis-escape mechanism (that permits eluding virus extinction despite replication in the presence of a mutagenic agent) and suggest that mutational bias can be a target of selection during virus replication.

PubMed: 28460010
DOI: 10.1093/gbe/evx075

実験手法

X-RAY DIFFRACTION (2.4 Å)