Why do two EF-Tu molecules act in the elongation cycle of

In the elongation cycle of bacterial protein biosynthesis, the binding of aminoacyl-tRNA (aa-tRNA) to the A-site of mRNA-programmed ribosomes is mediated by elongation factor Tu (EF-Tu) and associated with the hydrolysis of GTP. Recently, in the case of cognate aa-tRNA, the participation of two GTP molecules has been implicated in this reaction. These are likely to be involved in preventing the indiscriminate binding of aa-tRNA to the ribosomal A-site. This article integrates this unexpected finding with our current knowledge of the structure-function relationships of the macromolecules involved in the elongation cycle. terminus of the aa-tRNA in the A-site and the carboxyl terminus of the peptidyl-tRNA in the peptidyl-tRNA-binding (P)-site. The elongated peptidyl-tRNA bound to the A-site is translocated to the P-site and the deacylated tRNA is shifted from the P-site to the exit (E)site. During this process, the EF-Gbound GTP is hydrolysed, and the resulting EF-G-GDP leaves the ribosome. EF-Tu-GDP is recycled to its active state by EF-Ts, a GDP-to-GTP exchange factor. Poly(U)-directed poly(Phe) synthesis has been the model system used to study the basic steps of the elongation cycle, since it eliminates the need for specific initiation of polypeptide synthesis, and its codon-anticodon interaction is not subject to rejection by selection mechanisms.