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

Murina, Victoriia ; Kasari, Marje ; Takada, Hiraku ; Hinnu, Mariliis ; Saha, Chayan Kumar LU orcid ; Grimshaw, James W. ; Seki, Takahiro ; Reith, Michael ; Putrinš, Marta and Tenson, Tanel , et al. (2019) In Journal of Molecular Biology 431(18). p.3568-3590
Abstract

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... (More)

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.

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publishing date
type
Contribution to journal
publication status
published
keywords
ABCF, antibiotic resistance, ARE, ribosome, translation
in
Journal of Molecular Biology
volume
431
issue
18
pages
3568 - 3590
publisher
Elsevier
external identifiers
  • pmid:30597160
  • scopus:85060093624
ISSN
0022-2836
DOI
10.1016/j.jmb.2018.12.013
language
English
LU publication?
no
additional info
Funding Information: We gratefully acknowledge Fujio Kawamura for providing anti-L3 primary antibodies and Stijn Hendrik Peeters for constructing the pSHP2 plasmid. Thanks to Martin Carr for discussion and advice about eEF3 and EFL co-distribution. This work was supported by the Swedish Research Council ( 2015-04746 to G.C.A. and 2017-03783 to V.H.), Ragnar Söderberg Foundation (V.H.), Umeå Centre for Microbial Research (UCMR) gender policy program (G.C.A.), Carl Tryggers grants CTS 14:34 and CTS 15:35 (G.C.A.), Kempe Stiftelse grant JCK-1627 (G.C.A.), Jeanssons Stiftelse grant (G.C.A.), Molecular Infection Medicine Sweden (MIMS) (V.H.), postdoctoral grant from Umeå Centre for Microbial Research (UCMR) (H.T.), BBSRC grant BB/M011186/1 (J.W.G. and H.S.), Umeå Universitet Insamlingsstiftelsen för medicinsk forskning (G.C.A. and V.H.), and the European Regional Development Fund through the Centre of Excellence for Molecular Cell Technology (V.H. and T.T.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Funding Information: We gratefully acknowledge Fujio Kawamura for providing anti-L3 primary antibodies and Stijn Hendrik Peeters for constructing the pSHP2 plasmid. Thanks to Martin Carr for discussion and advice about eEF3 and EFL co-distribution. This work was supported by the Swedish Research Council (2015-04746 to G.C.A. and 2017-03783 to V.H.), Ragnar S?derberg Foundation (V.H.), Ume? Centre for Microbial Research (UCMR) gender policy program (G.C.A.), Carl Tryggers grants CTS 14:34 and CTS 15:35 (G.C.A.), Kempe Stiftelse grant JCK-1627 (G.C.A.), Jeanssons Stiftelse grant (G.C.A.), Molecular Infection Medicine Sweden (MIMS) (V.H.), postdoctoral grant from Ume? Centre for Microbial Research (UCMR) (H.T.), BBSRC grant BB/M011186/1 (J.W.G. and H.S.), Ume? Universitet Insamlingsstiftelsen f?r medicinsk forskning (G.C.A. and V.H.), and the European Regional Development Fund through the Centre of Excellence for Molecular Cell Technology (V.H. and T.T.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Author Contributions: G.C.A. conceived the study and carried out all the bioinformatic analyses except for sequence logo construction and eEF1A/EFL/eEF3 co-distribution analysis, which was carried out by C.K.S. V.H. V.M. M.K. H.S. H.T. T.T. and M.P. designed experimental analyses. V.M. M.K. H.T. M.H. T.S. M.R. H.S. and J.W.G. carried out the experiments. V.H. G.C.A. H.S. T.T. H.T. V.M. and M.K. analyzed the data. G.C.A. and V.H. drafted the manuscript with input from V.M. M.K. H.T. M.H. C.K.S. J.W.G. T.S. M.P. T.T. and H.S. Publisher Copyright: © 2018 The Author(s) Copyright: Copyright 2020 Elsevier B.V., All rights reserved.
id
e9f021e0-8d99-47e1-b3f1-922462a54941
date added to LUP
2021-09-24 20:34:34
date last changed
2024-06-16 19:30:42
@article{e9f021e0-8d99-47e1-b3f1-922462a54941,
  abstract     = {{<p>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.</p>}},
  author       = {{Murina, Victoriia and Kasari, Marje and Takada, Hiraku and Hinnu, Mariliis and Saha, Chayan Kumar and Grimshaw, James W. and Seki, Takahiro and Reith, Michael and Putrinš, Marta and Tenson, Tanel and Strahl, Henrik and Hauryliuk, Vasili and Atkinson, Gemma Catherine}},
  issn         = {{0022-2836}},
  keywords     = {{ABCF; antibiotic resistance; ARE; ribosome; translation}},
  language     = {{eng}},
  number       = {{18}},
  pages        = {{3568--3590}},
  publisher    = {{Elsevier}},
  series       = {{Journal of Molecular Biology}},
  title        = {{ABCF ATPases Involved in Protein Synthesis, Ribosome Assembly and Antibiotic Resistance : Structural and Functional Diversification across the Tree of Life}},
  url          = {{http://dx.doi.org/10.1016/j.jmb.2018.12.013}},
  doi          = {{10.1016/j.jmb.2018.12.013}},
  volume       = {{431}},
  year         = {{2019}},
}