5l3p › Citations

The stringent factor RelA adopts an open conformation on the ribosome to stimulate ppGpp synthesis.

Figure 1.
Figure 2.
Figure 3.
Arenz S, Abdelshahid M, Sohmen D, Payoe R, Starosta AL, Berninghausen O, Hauryliuk V, Beckmann R, Wilson DN
OpenAccess logo Nucleic Acids Res 44 6471-81 (2016)
Cited: 78 times
EuropePMC logo PMID: 27226493

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 >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.

Reviews - 5l3p mentioned but not cited (1)

  1. New perspectives on the molecular mechanisms of stress signalling by the nucleotide guanosine tetraphosphate (ppGpp), an emerging regulator of photosynthesis in plants and algae. Mehrez M, Romand S, Field B. New Phytol 237 1086-1099 (2023)

Articles - 5l3p mentioned but not cited (2)



Reviews citing this publication (16)

  1. The stringent response and physiological roles of (pp)pGpp in bacteria. Irving SE, Choudhury NR, Corrigan RM. Nat Rev Microbiol 19 256-271 (2021)
  2. Aminoacyl-tRNA synthetases. Rubio Gomez MA, Ibba M. RNA 26 910-936 (2020)
  3. Transcriptional Responses to ppGpp and DksA. Gourse RL, Chen AY, Gopalkrishnan S, Sanchez-Vazquez P, Myers A, Ross W. Annu Rev Microbiol 72 163-184 (2018)
  4. Make and break the alarmone: regulation of (p)ppGpp synthetase/hydrolase enzymes in bacteria. Ronneau S, Hallez R. FEMS Microbiol Rev 43 389-400 (2019)
  5. Triggering the stringent response: signals responsible for activating (p)ppGpp synthesis in bacteria. Irving SE, Corrigan RM. Microbiology (Reading) 164 268-276 (2018)
  6. Possible Roles for Basal Levels of (p)ppGpp: Growth Efficiency Vs. Surviving Stress. Fernández-Coll L, Cashel M. Front Microbiol 11 592718 (2020)
  7. The stringent response and Mycobacterium tuberculosis pathogenesis. Prusa J, Zhu DX, Stallings CL. Pathog Dis 76 (2018)
  8. The Ribosome as a Switchboard for Bacterial Stress Response. Cheng-Guang H, Gualerzi CO. Front Microbiol 11 619038 (2020)
  9. Emerging and divergent roles of pyrophosphorylated nucleotides in bacterial physiology and pathogenesis. Chau NYE, Ahmad S, Whitney JC, Coombes BK. PLoS Pathog 17 e1009532 (2021)
  10. Yeast as a Model to Understand Actin-Mediated Cellular Functions in Mammals-Illustrated with Four Actin Cytoskeleton Proteins. Akram Z, Ahmed I, Mack H, Kaur R, Silva RC, Castilho BA, Friant S, Sattlegger E, Munn AL. Cells 9 E672 (2020)
  11. Ribosomal Hibernation-Associated Factors in Escherichia coli. Maki Y, Yoshida H. Microorganisms 10 33 (2021)
  12. Understanding the Stringent Response: Experimental Context Matters. Dworkin J. mBio 14 e0340422 (2023)
  13. Many birds with one stone: targeting the (p)ppGpp signaling pathway of bacteria to improve antimicrobial therapy. Pulschen AA, Fernandes AZN, Cunha AF, Sastre DE, Matsuguma BE, Gueiros-Filho FJ. Biophys Rev 13 1039-1051 (2021)
  14. Awakening sleeper cells: a narrative review on bacterial magic spot synthetases as potential drug targets to overcome persistence. Veetilvalappil VV, Aranjani JM, Mahammad FS, Joseph A. Curr Genet 68 49-60 (2022)
  15. (p)ppGpp - an important player during heat shock response. Driller K, Cornejo FA, Turgay K. Microlife 4 uqad017 (2023)
  16. Recent functional insights into the magic role of (p)ppGpp in growth control. Mu H, Han F, Wang Q, Wang Y, Dai X, Zhu M. Comput Struct Biotechnol J 21 168-175 (2023)

Articles citing this publication (59)



Quick links