Mycoplasma penetrans Methionyl tRNA Synthetase is an Asymmetric Dimer fused to N-terminal Ancillary Domains

Diverse aminoacyl-tRNA synthetase (AARS) gene fusions are now recognized as a common mechanism for enhancing genetic diversity across all domains of life. The metS gene from Mycoplasma penetrans is a striking example of such an evolutionary mechanism because although M. penetrans has a condensed genome, the metS gene is nearly twice the size of a typical bacterial gene encoding methionyl tRNA synthetase (MetRS). We used cryo-EM to analyze the structure of the MpMetRS gene product to show that it is the product of three distinct enzyme domains: an N-terminal nucleotidyl transferase, a dimeric alanine-glyoxylate aminotransferase, and a MetRS. Only the N-terminal domains show two-fold symmetry, and the MetRS domain is only partially resolved. Modelling the full structure shows that a conformational change must occur to accommodate a tRNA-bound MetRS domain. A further rearrangement of the catalytic domains would also be necessary to bring the active sites adjacent to one another if this unique assembly of catalytic domains functions to channel substrates to MetRS.