The dimeric proto-ribosome: Structural details and possible implications on the origin of life

Abstract

A symmetric pocket-like entity, composed of two L-shaped RNA units, encircles the peptide synthesis site within the contemporary ribosome. This entity was suggested to be the vestige of a dimeric proto-ribosome, which could have formed spontaneously in the prebiotic world, catalyzing non-coded peptide bond formation and elongation. This structural element, beyond offering the initial step in the evolution of translation, is hypothesized here to be linked to the origin of life. By catalyzing the production of random peptide chains, the proto-ribosome could have enabled the formation of primary enzymes, launching a process of co-evolution of the translation apparatus and the proteins, thus presenting an alternative to the RNA world hypothesis.

Keywords: origin of life; proto-ribosome; ribosome symmetrical region.

Figure 1.

The proto-ribosome: (a) The suggested remnant of the proto-ribosome as appears within the ribosomal large subunit, projected approximately along the symmetry axis. The pocket was obtained by dimerization of the A-, P- core units (marked in blue and green, respectively. Same color scheme maintained in all figures), shown by their RNA backbone, with models of the amino acid reactants, as found in the crystal structure of the ribosomal large subunit of bacteria (Deinoccocus radiodurans, D50S, PDB code 1NJP) and archaea (Haloarcula marismortui, H50S, PDB code 1VQN) complexed with substrates mimicking the tip of tRNA 3′ end. The P-site amino acid in the D50S structure was derived from the A-site amino acid by applying the rotatory motion [5,6]. (b) 2D diagram of the symmetrical region from E. coli drawn in a manner portraying the 3D symmetry. The scheme shows phylogenetic conservation in 930 species from three domains and two organelles [12]. Nucleotides marked by capital A, C, G, and U are more than 98% conserved, while those depicted as points are less than 90% conserved. The 2D scheme of the proto-ribosome remnant, constructed from the two symmetry related ribosomal core units, each composed of two stems connected via a single stranded region, is shown on colored background.

Figure 2.

Secondary structure of L-shaped RNA molecules: (a) P-core unit from E.coli. Nucleotides marked by red letters were artificially added to the original ribosomal sequence, to complete truncated helices. H89 was closed by a GUGA tetraloop due to the symmetry relation to the GUGA loop of H93. Continuous and broken lines mark the two possible location of the 3′;5′ ends i.e. the elbow option and the tRNA-like options, repectively. (b) Right-angle tectoRNA molecule having the 3′:5′ at the elbow region [14] (c). L-shaped scheme of canonical tRNA (left) and mitochondrial tRNA possessing a flexible elbow angle (right) [21], having the 3′:5′ at the acceptor stem end.

Figure 3.

3D structure of L-shaped RNA molecules: H89 is shown in a vertical positioning (a) Overlap of the A- and P- core units from the structure of D50S (PDB code 1NKW), obtained by a rotation of 178.6° around the symmetry axis (LSQKAB program [27]). The projection direction is perpendicular to that shown in Figure 1a. (b) Comparison of the size and shape of the P- core unit (in green) and the tRNA (in light brown). (c) The anticodon helix of the tRNA molecule is overlapped on H89 of the P- core unit (stereo view).

Figure 4.

GNRA interaction motif joining the A-, P-core units within the contemporary ribosome (D50S PDB code 1NKW). The GUGA tetra stem loop of H93 (nucleotides G2595-A2598) interacts with a receptor region comprised of nucleotides from H74 (nucleotides G2436:C2073, A2435:U2074, U2075). A2598 makes an A-minor interaction with G2436:C2073.