1980 we detected a third tRNA binding site on E. coli ribosomes, the E site, in addition to A and P sites (ref. 14). It turned out that the existence of the E site is universal, since it was later also found with ribosomes from archaea (1986; 15) and eukarya (yeast, 1995; rabbit liver, 1997; 16,17). The detection of a reciprocal linkage between A and E sites led to the "allosteric three-site model" (1983, 1986; 18,19), which says that the occupation of the A site triggers the release of the E-tRNA (2006; 9) and vice versa, an occupation of the E site induces a low-affinity state for the ternary complex at the A site (Figure 1). This reciprocal linkage plays a key role for the accuracy and rate of protein synthesis (2006; 4) and explains the inhibition mechanisms of some antibiotics (e.g. edeine; 2004; 22). Furthermore, the fact that protein synthesis (elongation phase) always had at least two tRNAs on the ribosome, both interacting with the mRNA via codon-anticodon interaction, is instrumental for maintaining the reading frame (2004; 23; for review about the importance of the E site see Wilson and Nierhaus, 2006; 4).
Higher fungi such as yeast and Candida albicans contain a third essential elongation factor EF3 in addition to the two universal elongation factors EF-1 and EF-2. EF3 is the only ATPase involved in ribosomal elongation. We elucidated the function and importance of this factor in showing that the E-tRNA is so tightly bound that the A site cannot be occupied by a ternary complex in accord with the allosteric three-site model. It is the function of EF3ATP to open the E site thus allowing the E-tRNA release upon binding of the ternary complex aa-tRNAEF1AGTP to the A site (1995; 16).