Ribosomal tRNA binding sites: three-site models of translation

Abstract

The first models of translation described protein synthesis in terms of two operationally defined tRNA binding sites, the P-site for the donor substrate, the peptidyl-tRNA, and the A-site for the acceptor substrates, the aminoacyl-tRNAs. The discovery and analysis of the third tRNA 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 the three operationally defined sites in a simple fashion as three topographically fixed entities, thus leading to new concepts of tRNA binding and movement: (1) the hybrid-site model describes the tRNAs' movement through the ribosome in terms of changing binding sites on the 30S and 50S subunits in an alternating fashion. The tRNAs thereby pass through hybrid binding states. (2) The alpha-epsilon model introduces the concept of a movable tRNA-binding domain comprising two binding sites, termed alpha and epsilon. The translocation movement is seen as a result of a conformational change of the ribosome rather than as a diffusion process between fixed binding sites. The alpha-epsilon model reconciles most of the experimental data currently available.