RNA Therapeutics Institute; Department of Biochemistry and Molecular Pharmacology
Biophysics | Structural Biology
ArfA rescues ribosomes stalled on truncated mRNAs by recruiting release factor RF2, which normally binds stop codons to catalyze peptide release. We report two 3.2 A resolution cryo-EM structures - determined from a single sample - of the 70S ribosome with ArfA*RF2 in the A site. In both states, the ArfA C-terminus occupies the mRNA tunnel downstream of the A site. One state contains a compact inactive RF2 conformation. Ordering of the ArfA N-terminus in the second state rearranges RF2 into an extended conformation that docks the catalytic GGQ motif into the peptidyl-transferase center. Our work thus reveals the structural dynamics of ribosome rescue. The structures demonstrate how ArfA 'senses' the vacant mRNA tunnel and activates RF2 to mediate peptide release without a stop codon, allowing stalled ribosomes to be recycled.
ArfA, E. coli, biochemistry, biophysics, release factor 2, ribosome rescue, stalled ribosome, stop-codon-independent termination, structural biology
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Copyright © 2017, Demo et al.
DOI of Published Version
Elife. 2017 Mar 16;6. pii: e23687. doi: 10.7554/eLife.23687. Link to article on publisher's site
Demo G, Svidritskiy E, Madireddy R, Diaz-Avalos R, Grant T, Grigorieff N, Sousa D, Korostelev AA. (2017). Mechanism of ribosome rescue by ArfA and RF2. Open Access Articles. https://doi.org/10.7554/eLife.23687. Retrieved from https://escholarship.umassmed.edu/oapubs/3114
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