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Updated: Jun 11, 2026

Using SecM Arrest Sequence as a Tool to Isolate Ribosome Bound Polypeptides
09:42

Using SecM Arrest Sequence as a Tool to Isolate Ribosome Bound Polypeptides

Published on: June 19, 2012

Structural insights into YheS-mediated release of SecM-arrested ribosome

Kaishi Iso1, Toma Ikeda2, Kohei Yamasaki3

  • 1Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Tokyo, Japan.

Nature Communications
|June 9, 2026
PubMed

Insights

ATP-binding cassette subfamily F (ABCF) proteins help ribosomes overcome translation stalls. The YheS protein releases stalled ribosomes by repositioning the P-site tRNA, offering new insights into translation regulation.

Area of Science:

  • Molecular biology
  • Structural biology
  • Biochemistry

Background:

  • ATP-binding cassette subfamily F (ABCF) proteins are crucial for resolving ribosome stalling during translation.
  • Four ABCF proteins in E. coli (EttA, Uup, YbiT, YheS) facilitate translation of specific problematic nascent peptides.
  • The precise molecular mechanisms by which these proteins function remain largely unknown.

Purpose of the Study:

  • To elucidate the molecular mechanism of ribosome arrest release by the E. coli ABCF protein YheS.
  • To investigate how YheS interacts with the ribosome and nascent chain to resolve stalling induced by the SecM peptide.

Main Methods:

  • Cryo-electron microscopy (cryo-EM) to determine the structure of the ribosome-YheS complex.
  • Utilized an ATPase-deficient mutant of YheS for structural analysis.
  • Steered molecular dynamics simulations to support proposed mechanisms.

Main Results:

  • A 2.8 Å cryo-EM structure revealed YheS binding to the ribosomal E-site via the L1 stalk.
  • YheS's P-site tRNA-interaction motif (PtIM) displaces the P-site tRNA's CCA end near the peptidyl transferase center (PTC).
  • Cryo-EM density for the SecM nascent chain was lost upon YheS binding, indicating dissociation or destabilization within the exit tunnel.

Conclusions:

  • YheS relieves peptide sequence-dependent stalling by perturbing nascent chain-tunnel interactions.
  • This occurs through the relocation of the P-site tRNA, distinct from translocon-mediated release.
  • Provides mechanistic insight into a novel ribosome arrest release pathway.

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