Crystal structure of a complete threonyl tRNA synthetase: toggle clamp model?

To ensure high fidelity during protein translation, the majority of threonyl-tRNA synthetases (ThrRSs) utilize one of two types of editing domains at their N-termini to deacylate tRNAs mischarged with serine. To date, there have been few crystal structures of complete ThrRSs in the Protein Data Bank with their editing domains intact. Furthermore, there are no structures available of the complete enzyme in the apo form. Stenotrophomonas maltophilia ThrRS contains the HxxxH-type editing domain found in eukaryotes, eubacteria, and a subset of archaea. Here, we present a high-resolution crystal structure of the complete apo SmThrRS at 2.2Å resolution (PDB entry 6VU9) together with supporting small angle X-ray scattering data. The editing domain and a tRNA-binding β-hairpin in the catalytic domain are rotated away from each other in an open conformation, which is unfavorable for tRNA binding. The editing domain rotation is unique, and the structure contrasts with previously observed closed conformations showing the β-hairpin and hinge of the editing domain impinging on each other in the presence of substrates. On the basis of the available structures and sequence conservation at the engagement site, we consider a toggle clamp-like mechanism underlying the domain motions.