Signatures of tRNA Glx ‐specificity in proteobacterial glutamyl‐tRNA synthetases
Abstract The canonical function of glutamyl‐tRNA synthetase (GluRS) is to glutamylate tRNA Glu . Yet not all bacterial GluRSs glutamylate tRNA Glu ; many glutamylate both tRNA Glu and tRNA Gln , while some glutamylate only tRNA Gln and not the cognate substrate tRNA Glu . Understanding the basis of...
Saved in:
Published in | Proteins, structure, function, and bioinformatics |
---|---|
Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
12.11.2023
|
Online Access | Get full text |
Cover
Loading…
Summary: | Abstract
The canonical function of glutamyl‐tRNA synthetase (GluRS) is to glutamylate tRNA
Glu
. Yet not all bacterial GluRSs glutamylate tRNA
Glu
; many glutamylate both tRNA
Glu
and tRNA
Gln
, while some glutamylate only tRNA
Gln
and not the cognate substrate tRNA
Glu
. Understanding the basis of the unique specificity of tRNA
Glx
is important. Mutational studies have hinted at hotspot residues, both on tRNA
Glx
and GluRS, which play crucial roles in tRNA
Glx
‐specificity. However, its underlying structural basis remains unexplored. The majority of biochemical studies related to tRNA
Glx
‐specificity have been performed on GluRS from
Escherichia coli
and other proteobacterial species. However, since the early crystal structures of GluRS and tRNA
Glu
‐bound GluRS were from non‐proteobacterial species (
Thermus thermophilus
), proteobacterial biochemical data have often been interpreted in the context of non‐proteobacterial GluRS structures. Marked differences between proteobacterial and non‐proteobacterial GluRSs have been demonstrated; therefore, it is important to understand tRNA
Glx
‐specificity vis‐a‐vis proteobacterial GluRS structures. To this end, we solved the crystal structure of a double mutant GluRS from
E
.
coli
. Using the solved structure and several other currently available proteo‐ and non‐proteobacterial GluRS crystal structures, we probed the structural basis of the tRNA
Glx
‐specificity of bacterial GluRSs. Specifically, our analyses suggest a unique role played by the tRNA
Glx
D‐helix contacting loop of GluRS in the modulation of tRNA
Gln
‐specificity. While earlier studies have identified functional hotspots on tRNA
Glx
that control the tRNA
Glx
‐specificity of GluRS, this is the first report of complementary signatures of tRNA
Glx
‐specificity in GluRS. |
---|---|
ISSN: | 0887-3585 1097-0134 |
DOI: | 10.1002/prot.26634 |