Bacterial 70S ribosome nascent peptide exit tunnel (NPET)

The bacterial 70S ribosome nascent peptide exit tunnel (NPET) is a structural conduit within the large (50S) ribosomal subunit through which newly synthesized polypeptide chains travel to reach the cytoplasm [NIH, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4165058/]. Spanning approximately 100 Å in length, the tunnel is primarily composed of 23S ribosomal RNA (rRNA) and is constricted by loops of ribosomal proteins uL4 and uL22 [PNAS, https://www.pnas.org/doi/10.1073/pnas.1115951109]. Beyond serving as a passive channel, the NPET acts as a functional sensor that can interact with specific nascent peptide sequences to regulate translation through stalling mechanisms [NIH, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4165058/]. It is a critical therapeutic target for several classes of antibiotics, most notably macrolides (e.g., erythromycin, azithromycin), ketolides (e.g., telithromycin), and streptogramins B [MDPI, https://www.mdpi.com/2079-6382/13/10/928]. These drugs bind near the peptidyl transferase center (PTC) at the entrance of the tunnel, sterically blocking the elongation of the nascent chain and leading to the inhibition of bacterial protein synthesis [Nature Structural & Molecular Biology, https://www.nature.com/articles/nsmb.3031]. Resistance to these drugs often arises through modifications of the tunnel environment, such as methylation of the 23S rRNA or mutations in the ribosomal proteins that form the tunnel walls [PNAS, https://www.pnas.org/doi/10.1073/pnas.0808595105].

Other names

Nascent peptide exit tunnelRibosomal exit tunnelPolypeptide exit tunnelNPET

Antibiotics targeting the NPET bind to the 23S rRNA near the peptidyl transferase center (PTC), creating a steric block that prevents the passage of the nascent polypeptide chain [NIH, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4165058/]. This obstruction leads to the premature dissociation of peptidyl-tRNA or induces sequence-specific translation arrest (stalling), thereby halting protein synthesis and inhibiting bacterial growth [Nature Structural & Molecular Biology, https://www.nature.com/articles/nsmb.3031].