Mechanism of Elongation Factor G Function in tRNA Translocation on the Ribosome

The elongation cycle of ribosomal protein synthesis iscompleted by translocation, that is, the movement of thetRNA•mRNA complex on the ribosome. Translocation iscatalyzed by elongation factor G (EF-G) at the expense ofGTP. Early models of EF-G function and of the role ofGTP hydrolysis in translocation were based on two key results. One was that there is slow, spontaneous translocation, indicating that the reaction thermodynamically is exergonic without an additional energy source, such as GTPhydrolysis, and that the basic structural mechanism resides in the ribosome (Pestka 1969; Gavrilova and Spirin1972, 1974). Another was that the extent of EF-G-catalyzed translocation remained unchanged when GTP wasreplaced with nonhydrolyzable analogs, whereas the dissociation of EF-G from the ribosome was inhibited (Modolell et al. 1975; Belitsina et al. 1976). Thus, by analogywith the canonical GTPase switch mechanism, it was concluded that translocation is brought about by the bindingof EF-G•GTP to the ribosome, and that subsequent GTPhydrolysis is required for the dissociation of EF-G in theGDP-bound form (Kaziro 1978; Spirin 1985)...