The E. coli tRNA-Glu2-glutamyl tRNA-synthetase interaction was studied by analyzing the protected sites of the tRNA after digestion with T1-nuclease and RNase A as structural probes. The results showed that the acceptor-, D-, and anticodon-stems interact with the synthetase while the D-loop is unprotected. A conformational change could be detected in the D-loop and anticodonloop when the tRNA interacts with its cognate synthetase.