Abstract
Glycyl tRNA synthetase (GlyRS) provides a unique case among class II aminoacyl tRNA synthetases, with two clearly widespread types of enzymes: a dimeric (α2) species present in some bacteria, archaea, and eukaryotes; and a heterotetrameric form (α2β2) present in most bacteria. Although the differences between both types of GlyRS at the anticodon binding domain level are evident, the extent and implications of the variations in the catalytic domain have not been described, and it is unclear whether the mechanism of amino acid recognition is also dissimilar. Here, we show that the α-subunit of the α2β2 GlyRS from the bacterium Aquifex aeolicus is able to perform the first step of the aminoacylation reaction, which involves the activation of the amino acid with ATP. The crystal structure of the α-subunit in the complex with an analog of glycyl adenylate at 2.8 Å resolution presents a conformational arrangement that properly positions the cognate amino acid. This work shows that glycine is recognized by a subset of different residues in the two types of GlyRS. A structural and sequence analysis of class II catalytic domains shows that bacterial GlyRS is closely related to alanyl tRNA synthetase, which led us to define a new subclassification of these ancient enzymes and to propose an evolutionary path of α2β2 GlyRS, convergent with α2 GlyRS and divergent from AlaRS, thus providing a possible explanation for the puzzling existence of two proteins sharing the same fold and function but not a common ancestor.
Highlights
**Centre for Integrative Biology, Department of Integrated Structural Biology, Institute of Genetics and of Molecular and Cellular Biology, CNRS UMR 7104, 1 Rue Laurent Fries, Illkirch, France, and the ‡‡European Molecular Biology Laboratory, Hamburg
A structural and sequence analysis of class II catalytic domains shows that bacterial Glycyl tRNA synthetase (GlyRS) is closely related to alanyl tRNA synthetase, which led us to define a new subclassification of these ancient enzymes and to propose an evolution
The PCA analysis (Fig. 9) shows that only these two components, which together account for almost 50% of the structural variance of the core between the class II structures (Fig. 9B), allow us to define a clear separation between the subgroups, most importantly, the group formed by bacterial GlyRS and AlaRS and the rest of class II aaRSs (Figs. 9C and 10)
Summary
Bacterial GlyRS, belongs to the subclass IIc, together with PheRS, AlaRS, SepRS, and PylRS, the most heterogeneous group of the three subclasses [25,26,27]. A structural and sequence analysis performed on the activation domain of class II aaRS defines a new subclass IId, comprising AlaRS and bacterial ␣22 GlyRS. This modifies subclass IIc to contain (␣) PheRS, SepRS, and possibly PylRS. This classification standing on common structural motifs and active site residues in class IId enzymes allows us to propose a divergence of bacterial GlyRS from AlaRS, which resolves the puzzling existence of two proteins sharing the same fold and function but not a common ancestor
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