How do release factors recognize stop codons? Because release factors are entirely composed of protein, recognition of stop codons must be mediated by a protein-RNA interaction. Experiments in which short coding regions were genetically swapped between RFl and RF2 (which have different stop-codon specificity) pinpointed the region of this recognition to a stretch of three amino acids. Exchange of these three amino adds between RFl and RF2 results in hybrid release factors that acquire the stop codon recognition specificity of their counterpart but are otherwise identical in function. Evidently, just three amino acids are responsible for the specificity of stop codon recognition. The region defined by these three amino acids represents a peptide anticodon that interacts with and recognizes stop codons. In keeping with this view, the three-dimensional structure of RF2 bound to a ribosome reveals that the peptide anticodon is located close to the stop codon in the decoding center (Figure 14-36).
A region of class 1 release factors that contributes to polypeptide release has also been identified. All class I factors share n conserved, three-amino acid sequence (glycine glycine glutamics, GGQJ that is essential for polypeptide release. Moreover, the structure of RF2 bound to the ribosome confirms that the GGQ motif is located in close proximity to the peptidyl transferase center (Figure 14-36). It remains unclear whether the GGQ motif is directly involved in the hydrolysis of the polypeptide from the peptidyl-tRNA or if it induces a change m
FIGURE 14-36 Model of a type! release factor bound to the A site of the ribosome. This model illustrates the location of 3 class 1 release factor bound to the ribosome. ihe P site and E site tRIMAs are shown as L-shaped surfaces. The COQ amino acid motif that is involved in poplypeptide hydrolysis is located adjacent to the V end Of the P site iRNA. The SPF peptide anticodon is located adjacent to the anticodon loop of the P site tRNA in a position that would allow easy access to the stop codon. (Source: Adapted from Brodersen, D. E. and Ramaknshnan, V. 2003. Shape can be seductive. Wot. Struct £iro/. 10: 79, fig 2, part a.)
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