Role of Elongation Factors in Steering the Ribosomal Elongation Cycle

Abstract

The detection and characterization of the third transfer RNA (tRNA)-binding site on the ribosome, the E site, in addition to the classical A and P sites has led to the allosteric three-site model (ref. 1 and references therein), which has provided fresh impetus for discussion of and insights into the ribosomal elongation mechanism. It allows, for example, for the first time the identification of a common inhibition mechanism for aminoglycoside antibiotics,2 which do not exert their antibiotic activity by inducing misreading3 as previously assumed. The implications of the allosteric three-site model for the selection of the correct aminoacyl-tRNA and for the role of the elongation factors will be surveyed here. We start with a brief description of the main features of the allosteric three-site model, then address the problem of recognition involved in the selection of cognate aminoacyl-tRNAs and describe a surprising solution to this problem, which might be related to such fundamental structural features as the two-subunit nature of all ribosomes. We close the chapter with a first attempt to describe the mechanism of both elongation factors.