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GNAT toxins evolve toward narrow tRNA target specificities.

ABSTRACT: Type II toxin-antitoxin (TA) systems are two-gene modules widely distributed among prokaryotes. GNAT toxins associated with the DUF1778 antitoxins represent a large family of type II TAs. GNAT toxins inhibit cell growth by disrupting translation via acetylation of aminoacyl-tRNAs. In this work, we explored the evolutionary trajectory of GNAT toxins. Using LC/MS detection of acetylated aminoacyl-tRNAs combined with ribosome profiling, we systematically investigated the in vivo substrate specificity of an array of diverse GNAT toxins. Our functional data show that the majority of GNAT toxins are specific to Gly-tRNA isoacceptors. However, the phylogenetic analysis shows that the ancestor of GNAT toxins was likely a relaxed specificity enzyme capable of acetylating multiple elongator tRNAs. Together, our data provide a remarkable snapshot of the evolution of substrate specificity.

SUBMITTER: Bikmetov D

PROVIDER: S-EPMC9177977 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

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GNAT toxins evolve toward narrow tRNA target specificities.

Bikmetov Dmitry D Hall Alexander M J AMJ Livenskyi Alexei A Gollan Bridget B Ovchinnikov Stepan S Gilep Konstantin K Kim Jenny Y JY Larrouy-Maumus Gerald G Zgoda Viktor V Borukhov Sergei S Severinov Konstantin K Helaine Sophie S Dubiley Svetlana S

Nucleic acids research 20220601 10

Type II toxin-antitoxin (TA) systems are two-gene modules widely distributed among prokaryotes. GNAT toxins associated with the DUF1778 antitoxins represent a large family of type II TAs. GNAT toxins inhibit cell growth by disrupting translation via acetylation of aminoacyl-tRNAs. In this work, we explored the evolutionary trajectory of GNAT toxins. Using LC/MS detection of acetylated aminoacyl-tRNAs combined with ribosome profiling, we systematically investigated the in vivo substrate specifici ...[more]

PMID: 35609997

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Project description:Chemoreceptor-based signaling pathways are among the major modes of bacterial signal transduction, and Pseudomonas aeruginosa PAO1 is an important model to study their function. Of the 26 chemoreceptors of this strain, PctA has a broad ligand range and responds to most of the proteinogenic amino acids, whereas PctB and PctC have a much narrower range and show strong ligand preference for l-glutamine and γ-aminobutyrate, respectively. Using several comparative genomics approaches, we show that these receptors are paralogs: pctA gene duplication in the common ancestor of the genus Pseudomonas led to pctC, whereas pctB originated through another, independent pctA duplication in the common ancestor of P. aeruginosa Thus, the broad-range amino acid chemoreceptor was evolutionarily older, and chemoreceptors that complemented "missing" amino acid sensing abilities arose later in specific Pseudomonas lineages. Using comparative sequence analysis, newly solved crystal structures of PctA, PctB, and PctC ligand-binding domains, and their molecular dynamics simulations, we identified a conserved amino acid recognition motif and changes in the ligand-binding pocket that led to novel ligand specificities. In addition, we determined major forces driving the evolution of this group of chemoreceptors.IMPORTANCE Many bacteria possess a large number of chemoreceptors that recognize a variety of different compounds. More than 60% of the genomes analyzed in this study contain paralogous chemoreceptors, suggesting that they emerge with high frequency. We provide first insight on how paralogous receptors have evolved and show that two chemoreceptors with a narrow ligand range have evolved from an ancestral protein with a broad chemoeffector spectrum. Protein structures show that multiple changes in the ligand-binding site account for the differences in the ligand spectrum. This work lays the ground for further studies aimed at establishing whether the principles of ligand-binding evolution reported here can be generalized for a wider spectrum of sensory proteins in bacteria.

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GNAT toxins evolve toward narrow tRNA target specificities.

Publications

GNAT toxins evolve toward narrow tRNA target specificities.

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