Enzyme-substrate interactions in the Aspartyl tRNA synthetase system

It is accepted that tRNA recognition by aminoacyl-tRNA synthetases involves specific interactions between the protein and few bases of the nucleic acid called the identity determinants.. Other contacts have been observed with the sugar-phosphate backbone but could not be related to the specificity of the recognition process. The crystal structure of the non productive heterologous complex between yeast tRNA(Asp) and E. coli AspRS, together with those of the two corresponding homologous complexes, provide the first experimental evidence for an indirect readout of the first two base pairs of the acceptor stem through phosphate backbone-protein contacts. The structural correlation is confirmed by mutagenesis experiments at the tRNA level. A mechanism for tRNA induced AspRS activation can thus be proposed which accounts for all experimental observations and explains some otherwise unexplained sequence conservations.