Insights into Translational Termination from Crystal Structures of the 70S Ribosome Bound to Release Factor

Here we report high-resolution crystal structures of release factor 2 (RF2) bound to 70S ribosome. These structures emulate the translational states directly before and after hydrolysis of the ester bond in peptidyl-tRNA on the ribosome during translational termination. Our structures show detailed molecular interactions between the ribosome decoding center and RF2 upon stop-codon recognition. After a stop-codon is recognized, the universally conserved GGQ motif extends directly into the peptidyl transferase center forming a tightly packed catalytic core. Nucleotide A2602 in the 23S rRNA forms a favourable stack with the GGQ motif in RF2. The ribose of the A76 in the peptidyl-tRNA adopts C2’-endo conformation. Our structures help to rationalize a decade of biochemical and computational data on translational termination. Based on the structures, a mechanistic model on how the ester bond in the peptidyl tRNA is hydrolyzed is proposed.