Minireview Movement in ribosome translocation

Small GTPases play central roles in catalyzing each stage of protein synthesis on the ribosome. In prokaryotes, the relevant GTPases are: initiation factor IF2, which delivers the initiator tRNA to the P (peptide) site of the 30S ribosomal subunit; elongation factor EF-Tu, which delivers the aminoacyl-tRNA to the 70S ribosome (composed of 50S and 30S subunits); elongation factor EF-G, which promotes the translocation of tRNAs and the mRNA within the ribosome; and peptide release factor RF3, which promotes the dissociation of the release factors RF1 and RF2 following peptide release. These factors have been assumed to resemble classical GTPases, with the active form of the protein being the GTP binary complex. For example, the active EF-Tu•GTP complex binds aminoacyl-tRNA and transports it to the ribosome, which then stimulates the GTPase activity of EF-Tu (functioning as a GTPase-activator protein, or GAP) upon detection of a correct codon-anticodon interaction [1]. Following dissociation of EF-Tu•GDP from the ribosome, the GDP is exchanged for GTP in a guanine-nucleotide exchange reaction catalyzed by an elongation factor (EF-T) acting as a guanine-nucleotide exchange factor (GEF). For the other three factors, it is thought that the ribosome also provides the GAP function, whereas the requirement for a GEF has not been defined. The Ehrenberg group [2] recently discovered that the ribosome is in fact a GEF for the RF3 GTPase. Now, in Journal of Biology, the same group reports that the active form of EF-G for ribosome binding is the EF-G•GDP complex, not the EF-G•GTP complex, and that the ribosome acts as a GEF for EF-G as well [3]. Together with a number of other recent publications from the Ehrenberg, Frank, Wintermeyer and van Heel groups [4-6], these results shed new light on the roles of GTP and EF-G during the translocation reaction.