Peptidyl-tRNA Regulates the GTPase Activity of Translation Factors

Rapid protein synthesis in bacteria requires the G proteins IF2, EF-Tu, EF-G, and RF3. These factors catalyze all major steps of mRNA translation in a GTP-dependent manner. Here, it is shown how the position of peptidyl-tRNA in the ribosome and presence of its peptide control the binding and GTPase activity of these translation factors. The results explain how idling GTPase activity and negative interference between different translation factors are avoided and suggest that hybrid sites for tRNA on the ribosome play essential roles in translocation of tRNAs, recycling of class 1 release factors by RF3, and recycling of ribosomes back to a new round of initiation. We also propose a model for translocation of tRNAs in two separate steps, which clarifies the roles of EF-G•GTP and GTP hydrolysis in this process.