RIBOSOMAL TRANSFER-RNA BINDING-SITES - 3-SITE MODELS OF TRANSLATION

The first models of translation described protein synthesis in terms o f two operationally defined tRNA binding sites, the P-site for the don or substrate, the peptidyl-tRNA, and the A-site for the acceptor subst rates, the aminoacyl-tRNAs. The discovery and analysis of the third tR NA binding site, the E-site specific for deacylated tRNAs, resulted in the allosteric three-site model, the two major features of which are (1) the reciprocal relationship of A-site and E-site occupation, and ( 2) simultaneous codon-anticodon interactions of both tRNAs present at the elongating ribosome. However, structural studies do not support th e three operationally defined sites in a simple fashion as three topog raphically fixed entities, thus leading to new concepts of tRNA bindin g and movement: (1) the hybrid-site model describes the tRNAs' movemen t through the ribosome in terms of changing binding sites on the 30S a nd 50S subunits in an alternating fashion. The tRNAs thereby pass thro ugh hybrid binding states. (2) The a-E model introduces the concept of a movable tRNA-binding domain comprising two binding sites, termed a and E. The translocation movement is seen as a result of a conformatio nal change of the ribosome rather than as a diffusion process between fixed binding sites. The a-E model reconciles most of the experimental data currently available.