Protein synthesis takes place in four stages: initiation, elongation, termination and recycling. Elongation consists of delivery of a charged tRNA to the ribosome, peptide bond formation and translocation of the mRNA and tRNA, three steps forming a cyclic process, which is repeated for every amino acid added to a growing polypeptide chain. The result of the elongation cycle is the translation of the triplet genetic code contained in an mRNA, into the amino acid sequence of a protein. Since the 1960s it was appreciated that complex conformational changes must occur on the ribosome to accomplish translocation of mRNA and tRNA. Here I report x-ray crystallographic studies which shed light on how mRNA and tRNA are manipulated by the ribosome and mechanisms used by certain antibiotics to inhibit the elongation cycle of protein synthesis.

Specifically research reported here argue that tRNA translocation is a stepwise process that involves discrete structural intermediates of the ribosome. I report structural evidence that the antibiotics clindamycin and chloramphenicol inhibit protein synthesis by interfering with aminoacyl-tRNA positioning in the peptidyl transferase center. Also, I hypothesize based on structural data and phylogenetic analysis, that the identity of the ribosomal RNA residues numbered in E. coli 752, 2055 and 2609 contribute to the specificity of many antibiotics for binding to bacterial, rather than archaeal or eukaryotic ribosomes.