Minireview Ribosomal Tolerance and Peptide Bond Formation

GTP hydrolysis, for the translocation of the mRNA chain and the tRNA molecules. Analysis of the three-dimensional structures of unbound ribosomal subunits from eubacteria (Figure 1A; Schluenzen et al., 2000; Wimberly et al., 2000; Harms et al., 2001) and archaea (Ban et al., 2000) as well as of the entire ribosome (Yusupov et al., 2001) clearly showed that the centers of the major ribosomal activities, i.e. the decoding site in the small subunit and the peptide bond formation site in the large one, consist exclusively of ribosomal RNA (rRNA) (Ban et al., 2000; Nissen et al., 2000; Schluenzen et al., 2000; Wimberly et al., 2000; Harms et al., 2001; Bashan et al., 2003a). Hence, the primary actor in the main ribosomal functions is the rRNA, while ribosomal proteins may assist secondary activities, such as GTP hydrolysis and nascent proteins gating. Comparative studies revealed that ribosomal components of different sizes possess inherent conformational mobility, which could be correlated with their functional tasks (Schluenzen et al., 2000; Wimberly et al., 2000; Yusupov et al., 2001; Harms et al., 2001; Pioletti et al., 2001; Yonath, 2002a,b; Agmon et al., 2003; Bashan et al., 2003a; Berisio et al., 2003a). Among the large movable domains are the head and the platform of the small subunit, the two lateral protuberances of the large subunit (Figure 1A) and several intersubunit bridges, some of which may also assist tRNA translocation (Yonath, 2002a,b; Agmon et al., 2003). Of particular interest is the base of nucleotide A2602 (E. coli numbering system is used throughout), which was shown to have a critical role in tRNA 3’-end passage from the Ato the P-site (Agmon et al., 2003; Bashan et al., 2003a,b) as well as in the release of the nascent peptide during translation termination (Polacek et al., 2003).