The 2.0 Å crystal structure of Thermus thermophilus methionyl-tRNA synthetase reveals two RNA-binding modules

Background: The 20 aminoacyl-tRNA synthetases are divided into two classes, I and II. The 10 class I synthetases are considered to have in common the catalytic domain structure based on the Rossmann fold, which is totally different from the class II catalytic domain structure. The class I synthetases are further divided into three subclasses, a, b and c, according to sequence homology. No conserved structural features for tRNA recognition by class I synthetases have been established. Results: We determined the crystal structure of the class Ia methionyl-tRNA synthetase (MetRS) at 2.0 Å resolution, using MetRS from an extreme thermophile, Thermus thermophilus HB8. The T. thermophilus MetRS structure is in full agreement with the biochemical and genetic data from Escherichia coli MetRS. The conserved ‘anticodon-binding’ residues are spatially clustered on an α-helix-bundle domain. The Rossmann-fold and anticodon-binding domains are connected by a β–α–α–β–α topology (‘SC fold’) domain that contains the class I specific KMSKS motif. Conclusions: The α-helix-bundle domain identified in the MetRS structure is the signature of the class Ia enzymes, as it was also identified in the class Ia structures of the isoleucyl- and arginyl-tRNA synthetases. The β–α–α–β–α topology domain, which can now be identified in all known structures of the class Ia and Ib synthetases, is likely to dock with the inner side of the L-shaped tRNA, thereby positioning the anticodon stem.