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Title | Mechanism of release factor-mediated peptidyl-tRNA hydrolysis on the ribosome. |
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Journal, issue, pages | Science, Vol. 388, Issue 6753, Page eads9030, Year 2025 |
Publish date | Jun 19, 2025 |
![]() | Elena V Aleksandrova / Egor A Syroegin / Ritwika S Basu / Alexander A Vassilevski / Matthieu G Gagnon / Yury S Polikanov / ![]() ![]() |
PubMed Abstract | Translation termination is essential in all living organisms because it ensures that proteins have lengths strictly defined by their genes. This universal process is mediated by peptide release ...Translation termination is essential in all living organisms because it ensures that proteins have lengths strictly defined by their genes. This universal process is mediated by peptide release factors (RFs) that recognize stop codons and catalyze the hydrolysis of peptidyl transfer RNA (peptidyl-tRNA) on the ribosome, presumably by activating a water molecule. We report structures of the bacterial ribosome in complex with peptidyl-tRNA and RFs in the prepeptide release state. No hydrolytic water molecule was seen in the peptidyl transferase center. Instead, RFs induced rearrangements of the peptidyl-tRNA adenine 76 (A76) ribose pucker that orient the 2'-OH for the nucleophilic attack onto the neighboring carbonyl group. These findings suggest a catalytic mechanism of RF-mediated peptide release and provide a structural basis for the universal conservation of the catalytic domain in peptide RFs. |
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Methods | EM (single particle) / X-ray diffraction |
Resolution | 2.13 - 2.8 Å |
Structure data | EMDB-49594, PDB-9no7: ![]() PDB-9mtp: ![]() PDB-9mtq: ![]() PDB-9mtr: ![]() PDB-9mts: ![]() PDB-9mtt: |
Chemicals | ![]() ChemComp-MG: ![]() ChemComp-K: ![]() ChemComp-ZN: ![]() ChemComp-SF4: ![]() ChemComp-HOH: |
Source |
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![]() | RIBOSOME / Translation termination; peptide release; release factor; hydrolysis; peptidyl-tRNA; non-hydrolyzable; 70S ribosome; X-ray structure; pre-termination state; peptidyl transferase center / Translation termination; peptide release; release factor; hydrolysis; peptidyl-tRNA; 70S ribosome; cryo-EM; pre-termination state; peptidyl transferase center |