The LudP arrest peptide stalls translation by remodeling the ribosomal A-site

LudP, a SecDF-encoded arrest peptide conserved in Lacrimispora, induces robust Gram-positive-specific translation arrest via a 15-residue C-terminal element that remodels the ribosomal A-site.

• Why it matters: Evolutionarily diverse secretion-coupled arrest peptides must converge on equivalent physiological outcomes, but the shared mechanism and how peptide sequence dictates arrest stability and A-site selectivity were unclear.
• What they did: The authors combined in vitro and in vivo assays, systematic mutagenesis with deep mutational scanning, and cryo-electron microscopy to map a compact 15-residue C-terminal arrest element and its ribosome remodeling effects.
• The result: LudP’s nascent-chain -helix in the exit tunnel triggers Asp133-dependent conformational rearrangements of 23S rRNA (notably U2506), sterically and energetically destabilizing productive A-site aminoacyl-tRNA accommodation, supporting convergent evolution of secretion-coupled arrest peptides.