ABCF ATPases Involved in Protein Synthesis, Ribosome Assembly and Antibiotic Resistance: Structural and Functional Diversification across the Tree of Life

Victoriia Murina, Marje Kasari, Hiraku Takada, Mariliis Hinnu, Chayan Kumar Saha, James W. Grimshaw, Takahiro Seki, Michael Reith, Marta Putrinš, Tanel Tenson, Henrik Strahl, Vasili Hauryliuk, Gemma Catherine Atkinson*

*この研究の対応する著者

研究成果: Article査読

55 被引用数 (Scopus)

抄録

Within the larger ABC superfamily of ATPases, ABCF family members eEF3 in Saccharomyces cerevisiae and EttA in Escherichia coli have been found to function as ribosomal translation factors. Several other ABCFs including biochemically characterized VgaA, LsaA and MsrE confer resistance to antibiotics that target the peptidyl transferase center and exit tunnel of the ribosome. However, the diversity of ABCF subfamilies, the relationships among subfamilies and the evolution of antibiotic resistance (ARE) factors from other ABCFs have not been explored. To address this, we analyzed the presence of ABCFs and their domain architectures in 4505 genomes across the tree of life. We find 45 distinct subfamilies of ABCFs that are widespread across bacterial and eukaryotic phyla, suggesting that they were present in the last common ancestor of both. Surprisingly, currently known ARE ABCFs are not confined to a distinct lineage of the ABCF family tree, suggesting that ARE can readily evolve from other ABCF functions. Our data suggest that there are a number of previously unidentified ARE ABCFs in antibiotic producers and important human pathogens. We also find that ATPase-deficient mutants of all four E. coli ABCFs (EttA, YbiT, YheS and Uup) inhibit protein synthesis, indicative of their ribosomal function, and demonstrate a genetic interaction of ABCFs Uup and YheS with translational GTPase BipA involved in assembly of the 50S ribosome subunit. Finally, we show that the ribosome-binding resistance factor VmlR from Bacillus subtilis is localized to the cytoplasm, ruling out a role in antibiotic efflux.

本文言語English
ページ(範囲)3568-3590
ページ数23
ジャーナルJournal of Molecular Biology
431
18
DOI
出版ステータスPublished - 2019 8月 23
外部発表はい

ASJC Scopus subject areas

  • 生物理学
  • 構造生物学
  • 分子生物学

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