Bacterial pre-50S ribosomal subunit maturation intermediates (pre-50S)

Bacterial pre-50S ribosomal subunit maturation intermediates are the precursor complexes formed during the biogenesis of the large (50S) ribosomal subunit (Davis, J. H., & Williamson, J. R., 2017, Philosophical Transactions of the Royal Society B). This assembly process is a highly regulated pathway involving the folding of 23S and 5S ribosomal RNAs and the hierarchical binding of over 30 ribosomal proteins (Shajani, Z., et al., 2011, Annual Review of Biochemistry). These intermediates, often identified by sedimentation coefficients like 32S and 45S, represent discrete stages where the subunit is not yet catalytically active. In the context of disease, these intermediates are vital for the survival and proliferation of pathogenic bacteria, as they are the precursors to the protein-synthesizing machinery. Many clinically relevant antibiotics, including macrolides like erythromycin and ketolides like telithromycin, exert their effects not only by blocking the mature ribosome but also by binding to and destabilizing these assembly intermediates (Champney, W. S., 2001, Antimicrobial Agents and Chemotherapy). This binding prevents the transition to a functional 50S subunit, leading to a ribosome deficiency state in the bacterial cell. Research into these intermediates is expanding to identify novel small molecules that target assembly factors or specific RNA motifs unique to the immature state (Sohmen, D., et al., 2015, Nature Communications). Such strategies are particularly valuable for developing new classes of antimicrobials that can bypass traditional resistance mechanisms found in mature ribosomes.

Other names

50S assembly intermediatesImmature 50S ribosomal subunitspre-50S particlesBacterial large ribosomal subunit assembly intermediates

Inhibition of ribosomal subunit assembly by binding to nascent rRNA or ribosomal proteins, preventing the transition from intermediate particles to functional 50S subunits.