GTPase mechanisms and functions of translation factors on the ribosome

The elongation factors (EF) Tu and G and initiation factor 2 (IF2) from bac teria are multidomain GTPases with essential functions in the elongation an d initiation phases of translation. They bind to the same site on the ribos ome where their low intrinsic GTPase activities are strongly stimulated. Th e factors differ fundamentally from each other, and from the majority of GT Pases, in the mechanisms of GTPase control, the timing of P-i release, and the functional role of GTP hydrolysis. EF-Tu GTP forms a ternary complex wi th aminoacyl-tRNA, which binds to the ribosome, Only when a matching codon is recognized, the GTPase of EF-Tu is stimulated, rapid GTP hydrolysis and P-i release take place, EF-Tu rearranges to the GDP form, and aminoacyl-tRN A is released into the peptidyltransferase center. In contrast, EF-G hydrol yzes GTP immediately upon binding to the ribosome, stimulated by ribosomal protein L7/12. Subsequent translocation is driven by the slow dissociation of P-i, suggesting a mechano-chemical function of EF-G, Accordingly, differ ent conformations of EF-G on the ribosome are revealed by cryo-electron mic roscopy. GTP hydrolysis by IF2 is triggered upon formation of the 70S initi ation complex, and the dissociation of P-i and/or IF2 follows a rearrangeme nt of the ribosome into the elongation-competent state.