The 2.0 angstrom 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 Glass I synthetases are considered to have in common:the: catalytic domain structure based on the Rossmann fold, which is totally di fferent from the class II catalytic domain structure. The class I synthetas es are further divided,into three subclasses, a, b and c, according to sequ ence homology: No conserved structural features for tRNA recognition by cla ss I synthetases have been established. Results: We determined the crystal structure of the class la methionyl-tRNA synthetase (MetRS) at 2.0 Angstrom 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 Escherichi a coli MetRS. The conserved 'anticodon-binding' residues are spatially clus tered on an a-helix-bundle domain. The Rossmann-fold and anticodon-binding: domains are connected by a beta-alpha-alpha-beta-alpha topology ('SC fold' ) domain that contains the class 1 specific KMSKS motif, Conclusions: The ct-helix-bundle domain identified in the MetRS structure i s the signature of the class la enzymes, as it was also identified in:the c lass la structures of the isoleucyl- and arginyl-tRNA synthetases. The beta -alpha-alpha-beta-alpha topology domain, which can now be identified in all known structures of the class a and Ib synthetases, is likely to dock with the inner side Of the L-shaped tRNA, thereby positioning the anticodon ste m.