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TitleStructural insights into YheS-mediated release of SecM-arrested ribosome.
Journal, issue, pagesNat Commun, Vol. 17, Issue 1, Year 2026
Publish dateJun 9, 2026
AuthorsKaishi Iso / Toma Ikeda / Kohei Yamasaki / Yushin Ando / Fumiya K Sano / Tadaomi Furuta / Hideki Taguchi / Osamu Nureki / Yuhei Chadani / Yuzuru Itoh /
PubMed AbstractATP-binding cassette subfamily F (ABCF) proteins interact with the ribosome to resolve translation defects near the peptidyl transferase center (PTC). In Escherichia coli, four ABCF proteins (EttA, ...ATP-binding cassette subfamily F (ABCF) proteins interact with the ribosome to resolve translation defects near the peptidyl transferase center (PTC). In Escherichia coli, four ABCF proteins (EttA, Uup, YbiT, and YheS) selectively promote translation of distinct problematic nascent peptide sequences, but their molecular mechanisms remain unclear. Here, we present a 2.8 Å cryo-EM structure of the ribosome in complex with an ATPase-deficient mutant of YheS and investigate how it releases ribosomes arrested by the SecM nascent chain. YheS binds to the ribosomal E-site via the L1 stalk, and its P-site tRNA-interaction motif (PtIM) extends toward the PTC, displacing the CCA end of the P-site tRNA. Notably, the cryo-EM density corresponding to the SecM nascent chain within the exit tunnel is largely lost upon YheS binding. These observations suggest that YheS relieves peptide sequence-dependent stalling by perturbing nascent chain-tunnel interactions through P-site tRNA relocation. Steered molecular dynamics simulations provide qualitative support for this model. Together, our findings provide mechanistic insight into a mode of arrest release distinct from the translocon-mediated release mechanism.
External linksNat Commun / PubMed:42265116 / PubMed Central
MethodsEM (single particle)
Resolution2.75 - 2.89 Å
Structure data

EMDB-65381, PDB-9vvi:
Cryo-EM structure of SecM-arrested 70S ribosome with YheS
Method: EM (single particle) / Resolution: 2.82 Å

EMDB-66482: Cryo-EM structure of SecM-arrested 70S ribosome with YheS, the overall refined map
Method: EM (single particle) / Resolution: 2.82 Å

EMDB-66483: Cryo-EM structure of SecM-arrested 70S ribosome with YheS, local-masked refined map on LSU.
Method: EM (single particle) / Resolution: 2.75 Å

EMDB-66484: Cryo-EM structure of SecM-arrested 70S ribosome with YheS, local-masked refined map on the SSU body.
Method: EM (single particle) / Resolution: 2.84 Å

EMDB-66485: Cryo-EM structure of SecM-arrested 70S ribosome with YheS, local-masked refined map on the SSU head.
Method: EM (single particle) / Resolution: 2.89 Å

EMDB-66486: Cryo-EM structure of SecM-arrested 70S ribosome with YheS, local-masked refined map on YheS and L1 stalk.
Method: EM (single particle) / Resolution: 2.84 Å

EMDB-67339, PDB-9xwo:
Cryo-EM structure of SecM-arrested 70S ribosome (short SecM)
Method: EM (single particle) / Resolution: 2.89 Å

Chemicals

ChemComp-K:
Unknown entry

ChemComp-MG:
Unknown entry

ChemComp-SPD:
SPERMIDINE

ChemComp-ZN:
Unknown entry

ChemComp-ATP:
ADENOSINE-5'-TRIPHOSPHATE / ATP, energy-carrying molecule*YM

ChemComp-PRO:
PROLINE

ChemComp-HOH:
WATER

Source
  • escherichia coli (E. coli)
KeywordsRIBOSOME / SecM / ribosome arrest / ABCF

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