Peptidyl transferase activity is not mediated by any ribosomal proteins, but entirely byribosomal RNA (rRNA). The catalytic activity of the PTC is a significant piece of evidence supporting theRNA World hypothesis.[2] The PTC is a highly conserved region with a very slow rate of mutation. It is considered to be among the most ancient elements of the ribosome, predating thelast universal common ancestor.[3]
The position of the PTC is analogous in all ribosomes (domain V in 23S numbering), being a part of the large subunit ribosomal RNA with the name only varying due to the different size inSvedberg. It acts as a ribozyme at the lower tips (acceptor ends) of the A- and P- site tRNAs. The different names include:[4]: 1062
The substrates for the peptidyl transferase reaction are twotRNA molecules: one in thepeptidyl site, bearing the growing peptide chain, and the other in theaminoacyl site, bearing the amino acid that will be added to the chain. The peptidyl chain and the incoming amino acid are attached to their respective tRNAs viaester bonds to the oxygen atom at the3' ends of these tRNAs.[4]: 437–8 The 3' ends of all tRNAs share a universally conserved CCA sequence.[5] The alignment between the CCA ends of the ribosome-bound peptidyl tRNA and aminoacyl tRNA in the peptidyl transferase center contribute to peptide bond formation by providing the proper orientation for the reaction to occur.[6] This reaction occurs via nucleophilic displacement. The amino group of the aminoacyl tRNA attacks the terminal carbonyl group of the peptidyl tRNA. The reaction proceeds through a tetrahedral intermediate and the loss of the P site tRNA as a leaving group.[2]
In peptidyl-tRNA hydrolysis, the same mechanism is used, but with a water molecule as the nucleophile.[2]
Timing: Bokov and Steinberg (2009) "unwrapped" the 23S rRNA structure into several layers of contact. In their model, the PTC is the original element of 23S rRNA, to which structual features were later added.[7] An opposing view from Caetano-Anollés and Sun (2014) is that the tRNA's acceptor arm and the aaRS's catalytic domain came earlier than the genetic code and the PTC.[8]
Ancestor:
Tamura proposed in 2011 that the original PTC was formed by the concatenation of tRNAs. Farias et al. (2014) performedancestral sequence reconstruction on 22 types of tRNA and found a surprisingly high (for billions of years of divergence) 50.4% identity against the modern PTC ofThermus thermophilus, which is also identical in a few other thermophiles. The dinucleotide frequency was also similar across a wider range of bacteria.[9] Prosdocimi et al. (2020) compared a very large collection of PTCs to form an ancestral consensus. From 5'-to-3', the proto-bacterial-PTC is probably formed by the concatenation of tRNAPro, tRNATyr, tRNAPhe, tRNAGln, and tRNAGly. They also cite a few other earlier works on this topic not mentioned here.[10]
An alternative view is based on the PTC's pseudotwofold symmetry. A prototype might have just had one half of this system.[11] A 2022 study synthesized and tested a few "half-PTC" two-helix sequences. Some of them dimerize and form peptide bonds when tRNA is given.[12]
A designed minimized version ofE. coli PTC from 2024 was able to fold into a PTC-like shape without the help ofribosomal proteins and bind tRNA analogues at the P-site and the A-site. It fails to form peptide bonds due to binding the molecules in the wrong orientation.[3]
^abcdPolacek N, Mankin AS (January 2005). "The ribosomal peptidyl transferase center: structure, function, evolution, inhibition".Critical Reviews in Biochemistry and Molecular Biology.40 (5):285–311.doi:10.1080/10409230500326334.PMID16257828.
