The peptidyl transferase center (, PTC) is an aminoacyltransferase

ribozyme Ribozymes (ribonucleic acid enzymes) are RNA molecules that have the ability to Catalysis, catalyze specific biochemical reactions, including RNA splicing in gene expression, similar to the action of protein enzymes. The 1982 discovery of ribozy ...

(RNA enzyme) located in the large subunit of the

ribosome Ribosomes () are molecular machine, macromolecular machines, found within all cell (biology), cells, that perform Translation (biology), biological protein synthesis (messenger RNA translation). Ribosomes link amino acids together in the order s ...

. It forms

peptide bond In organic chemistry, a peptide bond is an amide type of covalent chemical bond linking two consecutive alpha-amino acids from C1 (carbon number one) of one alpha-amino acid and N2 (nitrogen number two) of another, along a peptide or protein cha ...

s between adjacent

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the 22 α-amino acids incorporated into proteins. Only these 22 a ...

s during the

translation Translation is the communication of the semantics, meaning of a #Source and target languages, source-language text by means of an Dynamic and formal equivalence, equivalent #Source and target languages, target-language text. The English la ...

process of

protein biosynthesis Protein biosynthesis, or protein synthesis, is a core biological process, occurring inside Cell (biology), cells, homeostasis, balancing the loss of cellular proteins (via Proteolysis, degradation or Protein targeting, export) through the produc ...

. It is also responsible for peptidyl-tRNA hydrolysis, allowing the release of the synthesized peptide chain at the end of translation. Peptidyl transferase activity is not mediated by any ribosomal proteins, but entirely by

ribosomal RNA Ribosomal ribonucleic acid (rRNA) is a type of non-coding RNA which is the primary component of ribosomes, essential to all cells. rRNA is a ribozyme which carries out protein synthesis in ribosomes. Ribosomal RNA is transcribed from ribosomal ...

(rRNA). The catalytic activity of the PTC is a significant piece of evidence supporting the

RNA World The RNA world is a hypothetical stage in the evolutionary history of life on Earth in which self-replicating RNA molecules proliferated before the evolution of DNA and proteins. The term also refers to the hypothesis that posits the existence ...

hypothesis. 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, probably predating the

last universal common ancestor The last universal common ancestor (LUCA) is the hypothesized common ancestral cell from which the three domains of life, the Bacteria, the Archaea, and the Eukarya originated. The cell had a lipid bilayer; it possessed the genetic code a ...

. 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 in

Svedberg In chemistry, a Svedberg unit or svedberg (symbol S, sometimes Sv) is a non- SI metric unit for sedimentation coefficients. The Svedberg unit offers a measure of a particle's size indirectly based on its sedimentation rate under acceleration ...

. It acts as a ribozyme at the lower tips (acceptor ends) of the A- and P- site tRNAs. The different names include: * Prokaryotes:

50S 50 S is the larger subunit of the 70S ribosome of prokaryotes, i.e. bacteria and archaea. It is the site of inhibition for antibiotics such as macrolides, chloramphenicol, clindamycin, and the pleuromutilins. It includes the 5S ribosom ...

ribosomal subunit, 23S rRNA * Eukaryotes: 60S ribosomal subunit, 28S rRNA ** See also: ,

mitochondrial ribosome The mitochondrial ribosome, or mitoribosome, is a protein complex that is active in mitochondria and functions as a riboprotein for translating mitochondrial mRNAs encoded in mtDNA. The mitoribosome is attached to the inner mitochondrial membra ...

, and . Peptidyl transferases are not limited to translation, but there are relatively few enzymes with this function.

Mechanism

The substrates for the peptidyl transferase reaction are two

tRNA Transfer ribonucleic acid (tRNA), formerly referred to as soluble ribonucleic acid (sRNA), is an adaptor molecule composed of RNA, typically 76 to 90 nucleotides in length (in eukaryotes). In a cell, it provides the physical link between the gene ...

molecules: one in the peptidyl site, bearing the growing peptide chain, and the other in the aminoacyl 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 via ester bonds to the oxygen atom at the 3' ends of these tRNAs. The 3' ends of all tRNAs share a universally conserved CCA sequence. 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. 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. In peptidyl-tRNA hydrolysis, the same mechanism is used, but with a water molecule as the nucleophile.

Evolution

Origin

''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. 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. ''Ancestor'': * Tamura proposed in 2011 that the original PTC was formed by the concatenation of tRNAs. Farias et al. (2014) performed ancestral 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 of ''Thermus thermophilus'', which is also identical in a few other thermophiles. The dinucleotide frequency was also similar across a wider range of bacteria. 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 tRNA^Pro, tRNA^Tyr, tRNA^Phe, tRNA^Gln, and tRNA^Gly. They also cite a few other earlier works on this topic not mentioned here. * An alternative view is based on the PTC's pseudotwofold symmetry. A prototype might have just had one half of this system. 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.

Minimization

A designed minimized version of ''E. coli'' PTC from 2024 was able to fold into a PTC-like shape without the help of

ribosomal protein A ribosomal protein (r-protein or rProtein) is any of the proteins that, in conjunction with rRNA, make up the ribosomal subunits involved in the cellular process of translation. ''E. coli'', other bacteria and Archaea have a 30S small subunit ...

s 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.

After the LUCA

Antibiotic inhibitors

The following

protein synthesis inhibitor A protein synthesis inhibitor is a compound that stops or slows the growth or proliferation of cells by disrupting the processes that lead directly to the generation of new proteins. While a broad interpretation of this definition could be used t ...

s target the peptidyl transferase center: *

Chloramphenicol Chloramphenicol is an antibiotic useful for the treatment of a number of bacterial infections. This includes use as an eye ointment to treat conjunctivitis. By mouth or by intravenous, injection into a vein, it is used to treat meningitis, pl ...

binds to residues A2451 and A2452 in the 23S rRNA of the ribosome and inhibits

formation. * Pleuromutilins also bind to the peptidyl transferase center. *

Macrolide Macrolides are a class of mostly natural products with a large macrocyclic lactone ring to which one or more deoxy sugars, usually cladinose and desosamine, may be attached. Macrolides belong to the polyketide class of natural products. ...

antibiotics are thought to inhibit peptidyl transferase, in addition to inhibiting ribosomal translocation.

References

External links

* {{Portal bar, Biology, border=no EC 2.3.2 Ribozymes Transferases