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TitleRibosome•RelA structures reveal the mechanism of stringent response activation.
Journal, issue, pagesElife, Vol. 5, Year 2016
Publish dateJul 19, 2016
AuthorsAnna B Loveland / Eugene Bah / Rohini Madireddy / Ying Zhang / Axel F Brilot / Nikolaus Grigorieff / Andrei A Korostelev /
PubMed AbstractStringent response is a conserved bacterial stress response underlying virulence and antibiotic resistance. RelA/SpoT-homolog proteins synthesize transcriptional modulators (p)ppGpp, allowing ...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 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.
External linksElife / PubMed:27434674 / PubMed Central
MethodsEM (single particle)
Resolution3.9 - 4.1 Å
Structure data

8279

5kps

EMDB-8279, PDB-5kps:
Structure of RelA bound to ribosome in absence of A/R tRNA (Structure I)
Method: EM (single particle) / Resolution: 3.9 Å

8280

5kpv

EMDB-8280, PDB-5kpv:
Structure of RelA bound to ribosome in presence of A/R tRNA (Structure II)
Method: EM (single particle) / Resolution: 4.1 Å

8281

5kpw

EMDB-8281, PDB-5kpw:
Structure of RelA bound to ribosome in presence of A/R tRNA (Structure III)
Method: EM (single particle) / Resolution: 3.9 Å

8282

5kpx

EMDB-8282, PDB-5kpx:
Structure of RelA bound to ribosome in presence of A/R tRNA (Structure IV)
Method: EM (single particle) / Resolution: 3.9 Å

Source
  • escherichia coli (strain k12) (bacteria)
  • escherichia coli k-12 (bacteria)
KeywordsRIBOSOME / RelA

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