Biology:Peptidyl transferase center

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Short description: Ribosomal component

Peptidyl transferase
Identifiers
EC number2.3.2.12
CAS number9059-29-4
Databases
IntEnzIntEnz view
BRENDABRENDA entry
ExPASyNiceZyme view
KEGGKEGG entry
MetaCycmetabolic pathway
PRIAMprofile
PDB structuresRCSB PDB PDBe PDBsum

The peptidyl transferase center (EC 2.3.2.12, PTC) is an aminoacyltransferase ribozyme (RNA enzyme) located in the large subunit of the ribosome. It forms peptide bonds between adjacent amino acids during the translation process of protein biosynthesis.[1] It is also responsible for peptidyl-tRNA hydrolysis, allowing the release of the synthesized peptide chain at the end of translation.[2]

Peptidyl transferase activity is not mediated by any ribosomal proteins, but entirely by ribosomal RNA (rRNA). The catalytic activity of the PTC is a significant piece of evidence supporting the RNA 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 the last 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 in Svedberg. It acts as a ribozyme at the lower tips (acceptor ends) of the A- and P- site tRNAs. The different names include:[4]: 1062 


Mechanism

The substrates for the peptidyl transferase reaction are two tRNA 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.[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]

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.[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) 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.[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]

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 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]

After the LUCA

Antibiotic inhibitors

The following protein synthesis inhibitors target the peptidyl transferase center:

See also

References

  1. ↑ "The Peptidyl Transferase Center: a Window to the Past". Microbiology and Molecular Biology Reviews 85 (4): e0010421. December 2021. doi:10.1128/MMBR.00104-21. PMID 34756086. Bibcode: 2021MMBR...85...21T. 
  2. ↑ 2.0 2.1 2.2 2.3 "The ribosomal peptidyl transferase center: structure, function, evolution, inhibition". Critical Reviews in Biochemistry and Molecular Biology 40 (5): 285–311. January 2005. doi:10.1080/10409230500326334. PMID 16257828. 
  3. ↑ 3.0 3.1 Tangpradabkul, Tiyaporn; Palo, Michael; Townley, Jill; Hsu, Kenneth B; participants, Eterna; Smaga, Sarah; Das, Rhiju; Schepartz, Alanna (9 February 2024). "Minimization of the E. coli ribosome, aided and optimized by community science". Nucleic Acids Research 52 (3): 1027–1042. doi:10.1093/nar/gkad1254. PMID 38214230. 
  4. ↑ 4.0 4.1 Biochemistry (5th ed.). Belmont CA: Brooks/Cole. 2012. ISBN 978-1-133-10629-6. 
  5. ↑ "CCA addition to tRNA: implications for tRNA quality control". IUBMB Life 62 (4): 251–260. April 2010. doi:10.1002/iub.301. PMID 20101632. 
  6. ↑ "After the ribosome structures: how does peptidyl transferase work?". RNA 9 (2): 155–159. February 2003. doi:10.1261/rna.2127103. PMID 12554855. 
  7. ↑ Bokov, Konstantin; Steinberg, Sergey V. (February 2009). "A hierarchical model for evolution of 23S ribosomal RNA". Nature 457 (7232): 977–980. doi:10.1038/nature07749. PMID 19225518. Bibcode: 2009Natur.457..977B. 
  8. ↑ Caetano-Anollés, Gustavo; Sun, Feng-Jie (9 May 2014). "The natural history of transfer RNA and its interactions with the ribosome". Frontiers in Genetics 5: 127. doi:10.3389/fgene.2014.00127. PMID 24847358. 
  9. ↑ Farias, Sávio T.; Rêgo, Thais G.; José, Marco V. (January 2014). "Origin and evolution of the Peptidyl Transferase Center from proto-tRNAs". FEBS Open Bio 4 (1): 175–178. doi:10.1016/j.fob.2014.01.010. PMID 24649398. 
  10. ↑ Prosdocimi, Francisco; Zamudio, Gabriel S.; Palacios-Pérez, Miryam; Torres de Farias, Sávio; V. José, Marco (5 August 2020). "The Ancient History of Peptidyl Transferase Center Formation as Told by Conservation and Information Analyses". Life 10 (8): 134. doi:10.3390/life10080134. PMID 32764248. Bibcode: 2020Life...10..134P. 
  11. ↑ "A vestige of a prebiotic bonding machine is functioning within the contemporary ribosome". Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences 366 (1580): 2972–2978. October 2011. doi:10.1098/rstb.2011.0146. PMID 21930590. 
  12. ↑ "Origin of life: protoribosome forms peptide bonds and links RNA and protein dominated worlds". Nucleic Acids Research 50 (4): 1815–1828. February 2022. doi:10.1093/nar/gkac052. PMID 35137169. 
  13. ↑ "Anti-peptidyl transferase leader peptides of attenuation-regulated chloramphenicol-resistance genes". Proceedings of the National Academy of Sciences of the United States of America 91 (12): 5612–5616. June 1994. doi:10.1073/pnas.91.12.5612. PMID 7515506. Bibcode: 1994PNAS...91.5612G. 
  14. ↑ "Interaction of pleuromutilin derivatives with the ribosomal peptidyl transferase center". Antimicrobial Agents and Chemotherapy 50 (4): 1458–1462. April 2006. doi:10.1128/AAC.50.4.1458-1462.2006. PMID 16569865. 
  15. ↑ "Protein synthesis inhibitors: macrolides mechanism of action animation. Classification of agents". Pharmamotion. The Community College of Baltimore County. http://pharmamotion.com.ar/protein-synthesis-inhibitors-macrolides-mechanism-of-action-animation-classification-of-agents/. 



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