The stringent factor RelA adopts an open conformation on the ribosome to stimulate ppGpp synthesis
Arenz, Stefan ; Abdelshahid, Maha ; Sohmen, Daniel ; Payoe, Roshani ; Starosta, Agata L. ; Berninghausen, Otto ; Hauryliuk, Vasili LU
; Beckmann, Roland
and Wilson, Daniel N.
(2016)
In Nucleic Acids Research
44(13).
p.6471-6481
- Abstract
Under stress conditions, such as nutrient starvation, deacylated tRNAs bound within the ribosomal A-site are recognized by the stringent factor RelA, which converts ATP and GTP/GDP to (p)ppGpp. The signaling molecules (p)ppGpp globally rewire the cellular transcriptional program and general metabolism, leading to stress adaptation. Despite the additional importance of the stringent response for regulation of bacterial virulence, antibiotic resistance and persistence, structural insight into how the ribosome and deacylated-tRNA stimulate RelA-mediated (p)ppGpp has been lacking. Here, we present a cryo-EM structure of RelA in complex with the Escherichia coli 70S ribosome with an average resolution of 3.7 Å and local resolution of 4 to... (More)
Under stress conditions, such as nutrient starvation, deacylated tRNAs bound within the ribosomal A-site are recognized by the stringent factor RelA, which converts ATP and GTP/GDP to (p)ppGpp. The signaling molecules (p)ppGpp globally rewire the cellular transcriptional program and general metabolism, leading to stress adaptation. Despite the additional importance of the stringent response for regulation of bacterial virulence, antibiotic resistance and persistence, structural insight into how the ribosome and deacylated-tRNA stimulate RelA-mediated (p)ppGpp has been lacking. Here, we present a cryo-EM structure of RelA in complex with the Escherichia coli 70S ribosome with an average resolution of 3.7 Å and local resolution of 4 to >10 Å for RelA. The structure reveals that RelA adopts a unique 'open' conformation, where the C-terminal domain (CTD) is intertwined around an A/T-like tRNA within the intersubunit cavity of the ribosome and the N-terminal domain (NTD) extends into the solvent. We propose that the open conformation of RelA on the ribosome relieves the autoinhibitory effect of the CTD on the NTD, thus leading to stimulation of (p)ppGpp synthesis by RelA.
(Less)
- author
- Arenz, Stefan
; Abdelshahid, Maha
; Sohmen, Daniel
; Payoe, Roshani
; Starosta, Agata L.
; Berninghausen, Otto
; Hauryliuk, Vasili
LU
; Beckmann, Roland
and Wilson, Daniel N.
- publishing date
- 2016
- type
- Contribution to journal
- publication status
- published
- in
- Nucleic Acids Research
- volume
- 44
- issue
- 13
- pages
- 6471 - 6481
- publisher
- Oxford University Press
- external identifiers
-
- pmid:27226493
- scopus:84982855956
- ISSN
- 0305-1048
- DOI
- 10.1093/nar/gkw470
- language
- English
- LU publication?
- no
- additional info
- Publisher Copyright: © 2016 The Author(s). Published by Oxford University Press on behalf of Nucleic Acids Research. Copyright: Copyright 2017 Elsevier B.V., All rights reserved.
- id
- 66219c48-c82e-4220-b4fc-0aaa469bbe9a
- date added to LUP
- 2021-09-24 20:42:26
- date last changed
- 2024-04-20 13:22:29
@article{66219c48-c82e-4220-b4fc-0aaa469bbe9a,
abstract = {{<p>Under stress conditions, such as nutrient starvation, deacylated tRNAs bound within the ribosomal A-site are recognized by the stringent factor RelA, which converts ATP and GTP/GDP to (p)ppGpp. The signaling molecules (p)ppGpp globally rewire the cellular transcriptional program and general metabolism, leading to stress adaptation. Despite the additional importance of the stringent response for regulation of bacterial virulence, antibiotic resistance and persistence, structural insight into how the ribosome and deacylated-tRNA stimulate RelA-mediated (p)ppGpp has been lacking. Here, we present a cryo-EM structure of RelA in complex with the Escherichia coli 70S ribosome with an average resolution of 3.7 Å and local resolution of 4 to >10 Å for RelA. The structure reveals that RelA adopts a unique 'open' conformation, where the C-terminal domain (CTD) is intertwined around an A/T-like tRNA within the intersubunit cavity of the ribosome and the N-terminal domain (NTD) extends into the solvent. We propose that the open conformation of RelA on the ribosome relieves the autoinhibitory effect of the CTD on the NTD, thus leading to stimulation of (p)ppGpp synthesis by RelA.</p>}},
author = {{Arenz, Stefan and Abdelshahid, Maha and Sohmen, Daniel and Payoe, Roshani and Starosta, Agata L. and Berninghausen, Otto and Hauryliuk, Vasili and Beckmann, Roland and Wilson, Daniel N.}},
issn = {{0305-1048}},
language = {{eng}},
number = {{13}},
pages = {{6471--6481}},
publisher = {{Oxford University Press}},
series = {{Nucleic Acids Research}},
title = {{The stringent factor RelA adopts an open conformation on the ribosome to stimulate ppGpp synthesis}},
url = {{http://dx.doi.org/10.1093/nar/gkw470}},
doi = {{10.1093/nar/gkw470}},
volume = {{44}},
year = {{2016}},
}