RNA Therapeutics Institute; Department of Biochemistry and Molecular Pharmacology
Amino Acids, Peptides, and Proteins | Bacteria | Biochemical Phenomena, Metabolism, and Nutrition | Biophysics | Cell Biology | Cells | Nucleic Acids, Nucleotides, and Nucleosides | Structural Biology
Protein synthesis ends when a ribosome reaches an mRNA stop codon. Release factors (RFs) decode the stop codon, hydrolyze peptidyl-tRNA to release the nascent protein, and then dissociate to allow ribosome recycling. To visualize termination by RF2, we resolved a cryo-EM ensemble of E. coli 70S*RF2 structures at up to 3.3 A in a single sample. Five structures suggest a highly dynamic termination pathway. Upon peptidyl-tRNA hydrolysis, the CCA end of deacyl-tRNA departs from the peptidyl transferase center. The catalytic GGQ loop of RF2 is rearranged into a long beta-hairpin that plugs the peptide tunnel, biasing a nascent protein toward the ribosome exit. Ribosomal intersubunit rotation destabilizes the catalytic RF2 domain on the 50S subunit and disassembles the central intersubunit bridge B2a, resulting in RF2 departure. Our structures visualize how local rearrangements and spontaneous inter-subunit rotation poise the newly-made protein and RF2 to dissociate in preparation for ribosome recycling.
E. coli, GGQ motif rearrangement, cell biology, ensemble cryo-EM, intersubunit rotation, molecular biophysics, release factor 2, ribosome recycling, structural biology, translation termination
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Copyright © 2019, Svidritskiy et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.
DOI of Published Version
Elife. 2019 Sep 12;8. pii: 46850. doi: 10.7554/eLife.46850. Link to article on publisher's site
Svidritskiy E, Demo G, Loveland AB, Xu C, Korostelev AA. (2019). Extensive ribosome and RF2 rearrangements during translation termination. Open Access Articles. https://doi.org/10.7554/eLife.46850. Retrieved from https://escholarship.umassmed.edu/oapubs/3976
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