The structural basis for release-factor activation during translation termination revealed by time-resolved cryogenic electron microscopy.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 31189921.
- Also identified by DOI 10.1038/s41467-019-10608-z and PMC identifier 6561943.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
When the ribosome encounters a stop codon, it recruits a release factor (RF) to hydrolyze the ester bond between the peptide chain and tRNA. RFs have structural motifs that recognize stop codons in the decoding center and a GGQ motif for induction of hydrolysis in the peptidyl transfer center 70 Å away. Surprisingly, free RF2 is compact, with only 20 Å between its codon-reading and GGQ motifs. Cryo-EM showed that ribosome-bound RFs have extended structures, suggesting that RFs are compact when entering the ribosome and then extend their structures upon stop codon recognition. Here we use time-resolved cryo-EM to visualize transient compact forms of RF1 and RF2 at 3.5 and 4 Å resolution, respectively, in the codon-recognizing ribosome complex on the native pathway. About 25% of complexes have RFs in the compact state at 24 ms reaction time, and within 60 ms virtually all ribosome-bound RFs are transformed to their extended forms.
Medical subject headings
- Escherichia coli Proteins
- Models, Molecular
- Peptide Chain Termination, Translational
- Peptide Termination Factors
- Protein Domains