Conformational Changes of Elongation Factor G on the Ribosome During tRNA Translocation

Summary The universally conserved GTPase elongation factor G (EF-G) catalyzes the translocation of transfer RNA (tRNA) and messenger RNA (mRNA) on the ribosome after peptide bond formation. Despite numerous studies suggesting that EF-G undergoes extensive conformational rearrangements during translocation, high resolution structures exist for essentially only one conformation of EF-G in complex with the ribosome. Here, we report four atomic resolution crystal structures of EF-G bound to the ribosome programmed in the pre- and post-translocational states and to the ribosome trapped by the antibiotic dityromycin. We observe a previously unseen conformation of EF-G in the pretranslocation complex, which is independently captured by dityromycin on the ribosome. Our structures provide insights into the conformational space that EF-G samples on the ribosome and reveal that tRNA translocation on the ribosome is facilitated by a structural transition of EF-G from a compact to an elongated conformation, which can be prevented by the antibiotic dityromycin.