Ribosome peptidyl transferase center – nascent peptide complex (PTC-NC)

The ribosome peptidyl transferase center (PTC) – nascent peptide complex is the catalytic core of the ribosome responsible for the formation of peptide bonds during protein synthesis (Steitz & Moore, 2003, DOI: 10.1016/S0968-0004(03)00171-6). This complex, primarily composed of ribosomal RNA (rRNA), acts as a ribozyme within the large ribosomal subunit to facilitate the transfer of the growing polypeptide chain from the peptidyl-tRNA to the incoming aminoacyl-tRNA (Polikanov et al., 2014, DOI: 10.1016/j.molcel.2014.09.020). The nascent peptide complex specifically describes the state where the newly synthesized polypeptide is threaded through the ribosomal exit tunnel, a path that can influence protein folding and translation rates (Wilson, 2014, DOI: 10.1038/nrmicro3355). As a primary therapeutic target, the PTC and its associated exit tunnel are the binding sites for numerous antibiotic classes, including macrolides, oxazolidinones, and pleuromutilins, which disrupt bacterial growth by stalling translation (Dunkle et al., 2010, DOI: 10.1126/science.1192661). In addition to antimicrobial therapy, this complex is a target for nonsense suppression agents like ataluren, which aim to treat genetic diseases by promoting the read-through of premature stop codons (Lentini et al., 2014, DOI: 10.1016/j.molmed.2014.01.010). However, the high conservation of the PTC across domains of life presents challenges, as some inhibitors can cross-react with human mitochondrial ribosomes, leading to clinical toxicities such as myelosuppression and neuropathy (Böttger et al., 2001, DOI: 10.1046/j.1365-2958.2001.02335.x). Understanding the structural dynamics of the PTC-nascent peptide interaction is essential for overcoming antibiotic resistance and developing precision medicines for translation-related pathologies.

Other names

Ribosomal peptidyl transferase centerPTCRibosome-nascent chain complexRNCLarge ribosomal subunit catalytic center50S peptidyl transferase center

Inhibition of peptide bond formation through competitive binding at the ribosomal A-site or P-site, or steric blockage of the nascent peptide exit tunnel to prevent polypeptide elongation.