Mechanism of release factor-mediated peptidyl-tRNA hydrolysis on the ribosome

• 成果类型: Article
• 署名作者: Aleksandrova, Elena V.; Syroegin, Egor A.; Basu, Ritwika S.; Vassilevski, Alexander A.; Gagnon, Matthieu G.; Polikanov, Yury S.
• 署名单位: University of Illinois System; University of Illinois Chicago; University of Illinois Chicago Hospital; University of Texas System; University of Texas Medical Branch Galveston; Russian Academy of Sciences; Pushchino Scientific Center for Biological Research (PSCBI) of the Russian Academy of Sciences; Institute of Bioorganic Chemistry of the Russian Academy of Sciences; University of Texas System; University of Texas Medical Branch Galveston; University of Texas System; University of Texas Medical Branch Galveston; University of Texas System; University of Texas Medical Branch Galveston; University of Illinois System; University of Illinois Chicago; University of Illinois Chicago Hospital; University of Illinois System; University of Illinois Chicago; University of Illinois Chicago Hospital
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-9321
• DOI: 10.1126/science.ads9030
• 发表日期: 2025-06-19
• 关键词: aminoacyl-transfer-rna; translation termination; crystal-structure; bond formation; factors rf1; stop codon; ggq motif; structural basis; molecular-basis; active-site

摘要

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.