General Targets of Ribosome

Decoding Center

The decoding center (DC) is the region comprising the A site on the 30S subunit that monitors the correct base pairing between the mRNA codon and the anticodon of the aa-tRNA. This part of the ribosome consists of regions of the 30S head and shoulder, and the top of helix 44 (h44) of 16S rRNA. Antibiotics belonging to several different chemical classes bind in the DC, and some of them are used to treat a broad range of infections.

Fig. 1 Visualization of the expansion segments on the 80S ribosome.¹

P and E sites in the 30S Subunit

The P and exit (E) sites in the 30S subunit refer to the locations occupied by the anticodon loops of the peptidyl- and deacyl-tRNAs, respectively, during translation. The E site is the third and final binding site for a tRNA before it dissociates from the ribosome. Antibiotics that bind to the P and E sites in the 30S subunit are generally referred to as translation initiation inhibitors, but some of them also affect tRNA and mRNA translocation.

Peptidyl Transferase Center

The majority of antibiotics bind to the 50S subunit cluster at the peptidyl transferase center, where the peptide bond formation occurs, and within the nascent peptide exit tunnel (NPET). Several of them inhibit protein synthesis by competing with the amino acid side chains of incoming aa-tRNAs for binding to the ribosome A-site crevice, the wedge-shaped gap formed by the bases of nucleotides U2504, A2451, and C2452 of the 23S rRNA.

Nascent Peptide Exit Tunnel

The nascent polypeptide chain remains attached to a tRNA molecule inside the ribosome at all times during translation until it is hydrolyzed by a release factor and released from the ribosome in response to a stop codon. During this process, a part of the synthesized polypeptide chain is located in the NPET (an important structural and functional element of the ribosome). The function of the exit tunnel appears not only to provide an unobstructed passage through the ribosome for newly synthesized polypeptide chains but also to regulate translation itself. Specific elements of the tunnel monitor the amino acid sequence of the nascent polypeptide chain, and arrest of the translation may occur in response to particular drugs or metabolites. The NPET is the target for many clinically important antibiotics, and its alteration can lead to antibiotic resistance in pathogenic bacteria.

Fig. 2 Exit tunnel‐occupying nascent polypeptides minimize the risk of intrinsic ribosome destabilization (IRD).²

Services at Creative Biolabs

Targets of ribosomes are the key to ribosome-based drug development. It is necessary to study the targets of ribosomes and the mechanism behind them deeper. As a global-leading CRO company, Creative Biolabs has invested a great deal of manpower, material, and financial resource in ribosome research. With these investments, we have accumulated extensive experience and successfully established a comprehensive ribosome technology platform. We are confident in providing global clients with high-quality ribosome-related services including but not limited to:

• Ribosome Separation and Extraction Services
• Ribosome Analysis Services
• Ribosomal Marker Antibody Development Services

If you are interested in our services, or you have any other problems during your ribosome studies, please don't hesitate to contact us for more information.

References

1. Hoffmann, Patrick C., et al. "Structures of the eukaryotic ribosome and its translational states in situ." Nature Communications 13.1 (2022): 7435.
2. Chadani, Yuhei, et al. "Nascent polypeptide within the exit tunnel stabilizes the ribosome to counteract risky translation." The EMBO Journal 40.23 (2021): e108299.