The Proto-Ribosome: an ancient nano-machine for peptide bond formation

Abstract

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 ribosomal functional centers involved in amino-acid polymerization. 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 performed 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 peptide bond formation as well as for substrate mediated catalysis. 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 similar manner to the modern PTC. Later in evolution, a mechanism, enabling some type of decoding genetic control triggered the emergence of the small ribosomal subunit or part of it. This seems to be the result of the appearance of reaction products that could have evolved after polypeptides capable of enzymatic function were generated sporadically, while an ancient stable RNA fold was converted into an old version of a tRNA molecule. As in the contemporary ribosome the symmetry relates only the backbone fold and nucleotides orientations but not nucleotide sequences, it emphasizes the superiority of functional requirement over sequence conservation, and indicates that the PTC may have evolved by gene fusion or gene duplication.

Keywords: RNA world; evolving ribosomes; peptide bond formation; polymerase; ribozyme.

Figure 1

Top: the symmetrical region within the large ribosomal subunit. Bottom: Schematic representation of ‘pocket-like’ proto-ribosome formation from a RNA precursor, showing simple catalytic peptidyl transferase activity.

Figure 2

Snapshots of the rotary motion, obtained by successive 18° rotations from A-to P-site (yellow to red color) of the 3’ end of ASM, around the bond connecting the 3'end with the rest of the tRNA molecule. The PTC boundaries scaffolding the path of the rotary motion. The positions of A2602 and U2585, the nucleotides that anchor the rotary motion are marked as well as the nucleotides that are in hydrogen bond contact with the tRNA 3’ end at the A and P-sites. The amino acids connected to the CCA end was removed from all snapshots, except for the initial and terminal ones, in order to minimize overlapping.