ABCF ATPases involved in protein synthesis, ribosome assembly and antibiotic resistance: structural and functional diversification across the tree of life

Abstract

Within the larger ABC superfamily of ATPases, ABCF family members eEF3 in Saccharomyces cerevisiae and EttA in Escherichia coli have been characterised as ribosomal translation factors.Several other ABCFs including VgaA and LsaA confer resistance to MLS-type ribosome-targeting antibiotics. 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 that there are 45 distinct subfamilies of ABCFs, which 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. This suggests that either antibiotic resistance is a general feature of bacterial ABCFs, or it is relatively easy to evolve antibiotic resistance from other ABCF functions. While eEF3 was thought to be fungi-specific, we have found eEF3-like factors in a range of single celled eukaryotes, suggesting an ancient origin in this domain of life. Finally, we address

Structural basis for bacterial ribosome quality control

“…B. subtilis and E. coli strains (Crowe-McAuliffe et al, 2018;Guerout-Fleury et al, 1996;Guerout-Fleury et al, 1995;Horinouchi and Weisblum, 1982;Murina et al, 2019;Takada et al, 2014) used in this study are listed in Table S3. All B. subtilis strains used were derivatives of the wild-type 168 strain.…”

Ribosome protection by ABC‐F proteins—Molecular mechanism and potential drug design

“…Ribosome protection, by which the drug is actively dislodged from its target site in ribosome by ATP‐binding cassette F (ABC‐F) protein, has recently become of great interest since many pathogenic bacteria and clinic isolates (including Staphylococcus aureus , Enterococcus faecalis , Listeria monocytogenes, Pseudomonas aeruginosa, and Escherichia coli ) have been reported to employ this mechanism …”

An ortholog of the Vasa intronic gene is required for small RNA-mediated translation repression in Chlamydomonas reinhardtii

“…In S. cerevisiae, Stm1 seems to influence the association of elongation factor eEF3 with ribosomes, a protein that both stimulates eEF1A-dependent binding of a cognate aminoacyl-tRNA to the ribosomal A site and facilitates the release of deacylated tRNA from the ribosomal E site (34,48). Although eEF3 was initially thought to be a fungal-specific translation factor, eEF3-like (eEF3L) proteins have now been identified in a wider range of eukaryotes (49). Chlamydomonas encodes 2 eEF3L homologs, containing the conserved domains involved in the interactions of yeast eEF3 with eEF1A and with the ribosome near the E site (48,49).…”

“…Although eEF3 was initially thought to be a fungal-specific translation factor, eEF3-like (eEF3L) proteins have now been identified in a wider range of eukaryotes (49). Chlamydomonas encodes 2 eEF3L homologs, containing the conserved domains involved in the interactions of yeast eEF3 with eEF1A and with the ribosome near the E site (48,49). Given the vig1 mutant hypersensitivity to cycloheximide, VIG1 may possibly modulate translation elongation (e.g., by influencing the activity/interactions of eEF3L factors) and/or the accessibility of cycloheximide to its site of action at the ribosomal E site (32).…”