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

Publication Type:

Journal Article

Authors:

Aleksandrova, Elena V; Syroegin, Egor A; Basu, Ritwika S; Vassilevski, Alexander A; Gagnon, Matthieu G; Polikanov, Yury S

Source:

Science, Volume 388, Issue 6753, p.eads9030 (2025)

Keywords:

Catalytic Domain, Codon, Terminator, Escherichia coli, Escherichia coli Proteins, Glutamine, Hydrolysis, Peptide Chain Termination, Translational, Peptide Termination Factors, Peptidyl Transferases, Ribosomes, RNA, Transfer, Amino Acyl, Thermus thermophilus

Abstract:

<p>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&#39;-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.</p>

PDB: 
9MTP, 9MTQ, 9MTR, 9MTS, 9MTT, 9NO7
Detector: 
EIGER2
Beamline: 
24-ID-C
24-ID-E