RNA Therapeutics Institute; Department of Biochemistry and Molecular Pharmacology
Biophysics | Structural Biology
Stringent response is a conserved bacterial stress response underlying virulence and antibiotic resistance. RelA/SpoT-homolog proteins synthesize transcriptional modulators (p)ppGpp, allowing bacteria to adapt to stress. RelA is activated during amino-acid starvation, when cognate deacyl-tRNA binds to the ribosomal A (aminoacyl-tRNA) site. We report four cryo-EM structures of E. coli RelA bound to the 70S ribosome, in the absence and presence of deacyl-tRNA accommodating in the 30S A site. The boomerang-shaped RelA with a wingspan of more than 100 A wraps around the A/R (30S A-site/RelA-bound) tRNA. The CCA end of the A/R tRNA pins the central TGS domain against the 30S subunit, presenting the (p)ppGpp-synthetase domain near the 30S spur. The ribosome and A/R tRNA are captured in three conformations, revealing hitherto elusive states of tRNA engagement with the ribosomal decoding center. Decoding-center rearrangements are coupled with the step-wise 30S-subunit 'closure', providing insights into the dynamics of high-fidelity tRNA decoding.
E. coli, RelA, biophysics, cognate tRNA, cryo-EM, decoding, ribosome, stringent response, structural biology
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Copyright © 2016, Loveland 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. 2016 Jul 19;5. pii: e17029. doi: 10.7554/eLife.17029. Link to article on publisher's site
Loveland AB, Bah E, Madireddy R, Zhang Y, Brilot AF, Grigorieff N, Korostelev AA. (2016). Ribosome*RelA structures reveal the mechanism of stringent response activation. Open Access Publications by UMass Chan Authors. https://doi.org/10.7554/eLife.17029. Retrieved from https://escholarship.umassmed.edu/oapubs/2789
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