A–DWhen aminoacyl‐tRNAs bind the ribosomal A‐site, the amino acid side chain is accommodated by the A‐site cleft—a hydrophobic cavity formed by universally conserved nucleotides A2820 and C2821 in the 25S rRNA in S. cerevisiae (A2451 and C2452 in E. coli 23S rRNA). The views compare the A‐site cleft of prokaryotic (A, C) and eukaryotic (B, D) ribosomes. In the vacant eukaryotic ribosome (A), the cleft is smaller compared to those in prokaryotes (B), which likely results from a A‐to‐U mutation of the adjacent rRNA nucleotide (U2822 in S. cerevisiae 25S rRNA). In the archaeal ribosome, the corresponding residue is represented by A2488 in H. marismortiu 23S rRNA (PDB ID 3cc2). In bacteria, it is represented by A2452 in E. coli 23S rRNA (PDB ID 4y4o). However, when the aminoacyl‐tRNA or its analog puromycin occupies the A‐site (C, D), the cleft adopts similar conformations in pro‐ and eukaryotic ribosomes. Consequently, the aminoacyl moiety has a similar position in the active site of prokaryotic and eukaryotic ribosome. Therefore, the structural organization of the A‐site cleft is highly evolutionary conserved, despite rRNA sequence variations between prokaryotes and eukaryotes.
