Bacterial 50S ribosomal subunit 23S rRNA nascent peptide exit tunnel (50S NPET)

The bacterial 50S ribosomal subunit 23S rRNA nascent peptide exit tunnel (NPET) is a structural conduit within the large ribosomal subunit that allows the growing polypeptide chain to emerge from the peptidyl transferase center (PTC) to the external environment (Wilson, D. N., 2014, Nature Reviews Microbiology). This tunnel is approximately 80 to 100 Å in length and is primarily composed of 23S ribosomal RNA, with contributions from ribosomal proteins L4 and L22 (Polikanov, Y. S., et al., 2018, Molecular Cell). Its primary biological function is to facilitate the orderly exit of nascent proteins while providing a microenvironment that can influence protein folding and translation kinetics (Kramer, G., et al., 2009, Nature Structural & Molecular Biology). The NPET is a critical pharmacological target for several classes of antibiotics, including macrolides, ketolides, and lincosamides (Gaynor, M., & Mankin, A. S., 2003, Current Topics in Medicinal Chemistry). These drugs bind to a specific pocket within the 23S rRNA near the PTC, physically obstructing the passage of the nascent peptide chain. This blockage leads to the stalling of translation and the eventual dissociation of the peptidyl-tRNA from the ribosome, effectively inhibiting bacterial protein synthesis (Vazquez-Laslop, N., & Mankin, A. S., 2018, Annual Review of Microbiology). Resistance to these drugs often arises through modifications of the 23S rRNA, such as methylation by Erm-family enzymes, which prevents drug binding (Vester, B., & Douthwaite, S., 2001, Antimicrobial Agents and Chemotherapy). Understanding the structural nuances of the NPET is essential for developing new antimicrobial agents that can overcome existing resistance mechanisms (Paukner, S., & Riedl, R., 2017, Cold Spring Harbor Perspectives in Medicine).

Other names

Nascent peptide exit tunnelNPETRibosomal exit tunnel23S rRNA exit tunnelPolypeptide exit tunnelBacterial 50S ribosomal subunit 23S rRNA nascent peptide exit tunnel near the peptidyl transferase center

Inhibition of bacterial protein synthesis by sterically blocking the passage of the nascent polypeptide chain through the ribosomal exit tunnel, leading to premature peptidyl-tRNA dissociation.