The LudP arrest peptide stalls translation by remodeling the ribosomal A-site
- 1University of Hamburg
Abstract
Bacterial ribosome arrest peptides couple translation to secretion and membrane homeostasis, providing an intracellular regulatory feedback system. Although several Sec/YidC-associated arrest peptides have been characterized, how evolutionarily diverse peptides converge on equivalent physiological outcomes remains unclear. Here we identify LudP (Lacrimispora upstream of secDF peptide), a previously unrecognized arrest peptide conserved in the genus Lacrimispora and encoded immediately upstream of secDF. In vitro and in vivo assays show that LudP induces robust Gram-positive-specific translation arrest that is released in a Sec signal-dependent manner. Using systematic mutagenesis and deep mutational scanning, we define a compact 15-residue C-terminal arrest element that governs arrest stability and A-site residue selectivity. Cryo-electron microscopy reveals that a LudP nascent-chain -helix in the exit tunnel remodels the peptidyltransferase center, with Asp133-dependent conformational rearrangements of 23S rRNA, notably U2506, sterically and energetically destabilizing productive A-site aminoacyl-tRNA accommodation. These findings support functional convergent evolution of secretion-coupled arrest peptides across bacterial lineages.
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BibTeX
@misc{gersteuer2026ludp,
title = {{The LudP arrest peptide stalls translation by remodeling the ribosomal A-site}},
author = {F. Gersteuer and Y. Harada and K. Fujiwara and H. Safdari and A. Harreither and L. Bock and D. N. Wilson and S. N. Chiba},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.26.761930},
url = {https://www.biorxiv.org/content/10.64898/2026.10.26.761930v1},
note = {CC BY-NC},
}
RIS
TY - UNPB
TI - The LudP arrest peptide stalls translation by remodeling the ribosomal A-site
AU - F. Gersteuer
AU - Y. Harada
AU - K. Fujiwara
AU - H. Safdari
AU - A. Harreither
AU - L. Bock
AU - D. N. Wilson
AU - S. N. Chiba
PY - 2026
DA - 2026/10/26
PB - bioRxiv
DO - 10.64898/2026.10.26.761930
UR - https://www.biorxiv.org/content/10.64898/2026.10.26.761930v1
AB - Bacterial ribosome arrest peptides couple translation to secretion and membrane homeostasis, providing an intracellular regulatory feedback system. Although several Sec/YidC-associated arrest peptides have been characterized, how evolutionarily diverse peptides converge on equivalent physiological outcomes remains unclear. Here we identify LudP (Lacrimispora upstream of secDF peptide), a previously unrecognized arrest peptide conserved in the genus Lacrimispora and encoded immediately upstream of secDF. In vitro and in vivo assays show that LudP induces robust Gram-positive-specific translation arrest that is released in a Sec signal-dependent manner. Using systematic mutagenesis and deep mutational scanning, we define a compact 15-residue C-terminal arrest element that governs arrest stability and A-site residue selectivity. Cryo-electron microscopy reveals that a LudP nascent-chain -helix in the exit tunnel remodels the peptidyltransferase center, with Asp133-dependent conformational rearrangements of 23S rRNA, notably U2506, sterically and energetically destabilizing productive A-site aminoacyl-tRNA accommodation. These findings support functional convergent evolution of secretion-coupled arrest peptides across bacterial lineages.
ER -