The SecM Arrest Peptide Traps a Pre-peptide Bond Formation State of the Ribosome

Overview

Journal Nat Commun

Specialty Biology

Date 2024 Mar 20

PMID 38503753

Authors

Felix Gersteuer

Martino Morici

Sara Gabrielli

Keigo Fujiwara

Haaris A Safdari

Helge Paternoga

Lars V Bock

Shinobu Chiba

Daniel N Wilson

Affiliations

Soon will be listed here.

Abstract

Nascent polypeptide chains can induce translational stalling to regulate gene expression. This is exemplified by the E. coli secretion monitor (SecM) arrest peptide that induces translational stalling to regulate expression of the downstream encoded SecA, an ATPase that co-operates with the SecYEG translocon to facilitate insertion of proteins into or through the cytoplasmic membrane. Here we present the structure of a ribosome stalled during translation of the full-length E. coli SecM arrest peptide at 2.0 Å resolution. The structure reveals that SecM arrests translation by stabilizing the Pro-tRNA in the A-site, but in a manner that prevents peptide bond formation with the SecM-peptidyl-tRNA in the P-site. By employing molecular dynamic simulations, we also provide insight into how a pulling force on the SecM nascent chain can relieve the SecM-mediated translation arrest. Collectively, the mechanisms determined here for SecM arrest and relief are also likely to be applicable for a variety of other arrest peptides that regulate components of the protein localization machinery identified across a wide range of bacteria lineages.

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