Aminoacyl-tRNA Synthetases in the Bacterial World

Abstract

Aminoacyl-tRNA synthetases (aaRSs) are modular enzymes globally conserved in the three kingdoms of life. All catalyze the same two-step reaction, i.e., the attachment of a proteinogenic amino acid on their cognate tRNAs, thereby mediating the correct expression of the genetic code. In addition, some aaRSs acquired other functions beyond this key role in translation. Genomics and X-ray crystallography have revealed great structural diversity in aaRSs (e.g., in oligomery and modularity, in ranking into two distinct groups each subdivided in 3 subgroups, by additional domains appended on the catalytic modules). AaRSs show huge structural plasticity related to function and limited idiosyncrasies that are kingdom or even species specific (e.g., the presence in many Bacteria of non discriminating aaRSs compensating for the absence of one or two specific aaRSs, notably AsnRS and/or GlnRS). Diversity, as well, occurs in the mechanisms of aaRS gene regulation that are not conserved in evolution, notably between distant groups such as Gram-positive and Gram-negative Bacteria. The review focuses on bacterial aaRSs (and their paralogs) and covers their structure, function, regulation, and evolution. Structure/function relationships are emphasized, notably the enzymology of tRNA aminoacylation and the editing mechanisms for correction of activation and charging errors. The huge amount of genomic and structural data that accumulated in last two decades is reviewed, showing how the field moved from essentially reductionist biology towards more global and integrated approaches. Likewise, the alternative functions of aaRSs and those of aaRS paralogs (e.g., during cell wall biogenesis and other metabolic processes in or outside protein synthesis) are reviewed. Since aaRS phylogenies present promiscuous bacterial, archaeal, and eukaryal features, similarities and differences in the properties of aaRSs from the three kingdoms of life are pinpointed throughout the review and distinctive characteristics of bacterium-like synthetases from organelles are outlined.

The complex evolutionary history of aminoacyl-tRNA synthetases

“…Nevertheless, the integration of available knowledge about known AARS paralogs with such resistance, together with the extent of paralog presence in prokaryotic genomes, as shown in Table 1, does not provide strong support for such a claim. An alternative explanation is that these paralogs are involved in other biochemical functions (65), many of them as yet unknown, in accordance with various observations where AARSs form complexes with other types of proteins, thus participating in other functions beyond translation (22,66). It is also intriguing that atypical AARS paralogs have been identified as participating in peptide formation via the non-ribosomal peptide synthesis mechanism (67).…”

Arabidopsis seryl‐tRNA synthetase: the first crystal structure and novel protein interactor of plant aminoacyl‐tRNA synthetase

“…Aminoacyl‐tRNA synthetases (aaRSs) are essential cellular enzymes that link a specific amino acid to the cognate tRNA and act as translators of the genetic code . As a class of housekeeping enzymes participating in translation, aaRSs are now known to be involved also in other essential cellular processes, such as transcription, splicing, signal transduction, inflammation, angiogenesis, and apoptosis .…”

Hierarchical groove discrimination by Class I and II aminoacyl-tRNA synthetases reveals a palimpsest of the operational RNA code in the tRNA acceptor-stem bases

“…Crystal structures of aaRS•tRNA complexes ( 12 ) have contributed two essential qualitative aspects of recognition. (i) Class II aaRS bind to the tRNA major groove in a manner that does not distort the 3′ acceptor terminus, whereas Class I aaRS approach via the minor groove and thus must somehow distort the tRNA 3′-terminus into a hairpin, allowing the terminal adenosine to turn back into the aaRS active site, which leads to acylation of the 2′-, rather than the 3′-OH group.…”