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Extensive ribosome and RF2 rearrangements during translation termination.
Elife 2019; 8E

Abstract

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 Å 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 β-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.

Authors+Show Affiliations

RNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, United States.RNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, United States.RNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, United States.Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, United States.RNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, United States. Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, United States.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

31513010

Citation

Svidritskiy, Egor, et al. "Extensive Ribosome and RF2 Rearrangements During Translation Termination." ELife, vol. 8, 2019.
Svidritskiy E, Demo G, Loveland AB, et al. Extensive ribosome and RF2 rearrangements during translation termination. Elife. 2019;8.
Svidritskiy, E., Demo, G., Loveland, A. B., Xu, C., & Korostelev, A. A. (2019). Extensive ribosome and RF2 rearrangements during translation termination. ELife, 8, doi:10.7554/eLife.46850.
Svidritskiy E, et al. Extensive Ribosome and RF2 Rearrangements During Translation Termination. Elife. 2019 09 12;8 PubMed PMID: 31513010.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Extensive ribosome and RF2 rearrangements during translation termination. AU - Svidritskiy,Egor, AU - Demo,Gabriel, AU - Loveland,Anna B, AU - Xu,Chen, AU - Korostelev,Andrei A, Y1 - 2019/09/12/ PY - 2019/03/14/received PY - 2019/08/28/accepted PY - 2019/9/13/entrez PY - 2019/9/13/pubmed PY - 2019/9/13/medline KW - E. coli KW - GGQ motif rearrangement KW - cell biology KW - ensemble cryo-EM KW - intersubunit rotation KW - molecular biophysics KW - release factor 2 KW - ribosome recycling KW - structural biology KW - translation termination JF - eLife JO - Elife VL - 8 N2 - 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 Å 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 β-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. SN - 2050-084X UR - https://www.unboundmedicine.com/medline/citation/31513010/Extensive_ribosome_and_RF2_rearrangements_during_translation_termination L2 - https://doi.org/10.7554/eLife.46850 DB - PRIME DP - Unbound Medicine ER -