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Ribosome•RelA structures reveal the mechanism of stringent response activation

TitleRibosome•RelA structures reveal the mechanism of stringent response activation
Publication TypeJournal Article
Year of Publication2016
AuthorsLoveland, AB, Bah E, Madireddy R, Zhang Y, Brilot AF, Grigorieff N, Korostelev AA
Refereed DesignationRefereed
Date Published07/2016

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 stresses. RelA is activated during amino-acid starvation, when cognate deacyl-tRNA binds to the ribosomal A (aminoacyltRNA) 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 Å 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.

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