Ribosomes Left in the Dust: Diverse Strategies for Peptide-Mediated Translation Stalling

摘要

Ribosomes are fast, accurate, and highly processive enzymes. While the ribosome translates the vast majority of the prote-ome efficiently, certain polypeptide sequences stall the ribosome either on their own or in combination with a small molecule (Cruz-Vera et al., 2011). Moreover, a number of biological processes have evolved to rely on these peptide-medi-ated stalling events for their functionality, including the induction of erythromycin/ macrolide resistance (ErmC), regulation of intracellular tryptophan levels (TnaC), and modulation of the SecA secretory system (SecM). Over the years, a number of studies have identified many of the key residues in both the peptides and ribosome exit tunnel that contribute to pausing. However, what has remained unclear is how these interactions affect the structure of the ribosome and in particular the peptidyl-transferase center (PTC) to prevent further elongation or termination. Two recent papers in Molecular Cell (Arenz et al., 2014a) and Cell Reports (Bischoff et al., 2014) harness the power of recent advances in cryo-EM to address these issues. Both groups report high-resolution cryo-EM maps of peptide-stalled ribosomes that help to shed light on the interactions and mechanisms that nascent peptides utilize to mediate these events.