The Proto-Ribosome: An Ancient Nano-machine for Peptide Bond Formation

The ribosome is a ribozyme whose active site, the peptidyl transferase center (PTC), is situated within a highly conserved universal symmetrical region that connects all ri- bosomal functional centers involved in amino acid polymeri- zation. The linkage between this elaborate architecture and A-site tRNA position revealed that the A- to P-site passage of the tRNA 3' terminus during protein synthesis is per- formed by a rotary motion, synchronized with the overall tRNA/mRNA sideways movement, and guided by the PTC. This rotary motion leads to suitable stereochemistry for pep- tide bond formation as well as for substrate-mediated catal- ysis. Analysis of the substrate binding modes to ribosomes led to the hypothesis that the ancient ribosome produced single peptide bonds and non-coded chains, potentially in a simi- lar manner to the modern PTC. Later in evolution, a mecha- nism, enabling some type of decoding genetic control trig- gered the emergence of the small ribosomal subunit or part of it. This seems to be the result of the appearance of reac- tion products that could have evolved after polypeptides ca- pable of enzymatic function were generated sporadically, while an ancient stable RNA fold was converted into an old version of a tRNA molecule. Since in the contemporary ribo- some, the symmetry relates only to the backbone fold and nucleotide orientations but not nucleotide sequences, it em- phasizes the superiority of functional requirement over se- quence conservation, and indicates that the PTC may have evolved by gene fusion or gene duplication.