engleski

New links between protein biosynthesis and nonribosomal peptide synthesis

Aminoacyl-tRNA synthetases (aaRS) catalyze ATP-dependent attachment of amino acids to tRNA in protein synthesis. Similar role play adenylation domains in template independent nonribosomal peptide synthesis (NRPS), by attachment of activated precursors to dedicated carrier proteins. Although they catalyze analogous reactions in mechanistically similar manner, using aminoacyl-adenylates as intermediates, adenylation domains and aaRS are structurally and evolutionary unrelated. The genomes of many bacteria are sprinkled with putative ORFs encoding the proteins homologous to class II aaRS catalytic core, but lacking tRNA binding domain. We have cloned and characterized three such aaRS truncated homologs. Sequence analysis shows clear homology, while crystal structure determination confirmed remarkable structural similarity to seryl-tRNA synthetases (SerRS) from methanogenic archaea. In spite of close resemblance to SerRS, these enzymes have different amino acid specificity. Even more surprising, the SerRS homologs do not aminoacylate tRNA, but instead they transfer amino acids to thiol group of phosphopantetheinyl prosthetic arm of carrier proteins found in their genomic vicinity. Thus, the reaction they catalyze is essentially the same as the reaction catalyzed by adenylation domains in NRPS. It has been long speculated about possible evolutionary relations between programmed ribosomal protein synthesis and template independent NRPS, based on weak thiol acylation activity of contemporary aaRS. Our findings of SerRS homologs engaged exclusively in carrier protein acylation and thioester bond formation provide direct experimental evidence that further supports this hypothesis.

seryl-tRNA synthetase; aaRS homologs; amino acid:[carrier protein] ligase; carrier protein; noncanonical functions of aaRS

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