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J Mol Biol. 2018 Dec 28. pii: S0022-2836(18)31288-9. doi: 10.1016/j.jmb.2018.12.013. [Epub ahead of print]

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

Author information

1
Department of Molecular Biology, Umeå University, 901 87, Umeå, Sweden; Laboratory for Molecular Infection Medicine Sweden (MIMS), Umeå University, 901 87, Umeå, Sweden.
2
Department of Molecular Biology, Umeå University, 901 87, Umeå, Sweden.
3
University of Tartu, Institute of Technology, Nooruse 1, 50411 Tartu, Estonia.
4
Centre for Bacterial Cell Biology, Institute for Cell and Molecular Biosciences Newcastle University, Richardson Road, Newcastle upon Tyne, NE2 4AX, United Kingdom.
5
Department of Applied Chemistry and Biotechnology, Faculty of Engineering, Chiba University, 263-8522, Chiba, Japan.
6
Department of Molecular Biology, Umeå University, 901 87, Umeå, Sweden; Laboratory for Molecular Infection Medicine Sweden (MIMS), Umeå University, 901 87, Umeå, Sweden; University of Tartu, Institute of Technology, Nooruse 1, 50411 Tartu, Estonia.
7
Department of Molecular Biology, Umeå University, 901 87, Umeå, Sweden. Electronic address: gemma.atkinson@umu.se.

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 characterised VgaA, LsaA and MsrE confer resistance to antibiotics that target the peptidyl transferase centre and exit tunnel of the ribosome. However, the diversity of ABCF subfamilies, the relationships among subfamilies and the evolution of antibiotic resistance factors from other ABCFs have not been explored. To address this, we analysed 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 they were present in the last common ancestor of both. Surprisingly, currently known antibiotic resistance (ARE) ABCFs are not confined to a distinct lineage of the ABCF family tree, suggesting antibiotic resistance can readily evolve from other ABCF functions. Our data suggest 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 localised to the cytoplasm, ruling out a role in antibiotic efflux.

KEYWORDS:

ABCF; ARE; antibiotic resistance; ribosome; translation

PMID:
30597160
DOI:
10.1016/j.jmb.2018.12.013
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