6qg6 › Citations

Structural basis for the inhibition of translation through eIF2α phosphorylation.

Fig. 1
Fig. 2
Fig. 3
Gordiyenko Y, Llácer JL, Ramakrishnan V
OpenAccess logo Nat Commun 10 2640 (2019)
Related entries: 6qg0, 6qg1, 6qg2, 6qg3, 6qg5

Cited: 35 times
EuropePMC logo PMID: 31201334

Abstract

One of the responses to stress by eukaryotic cells is the down-regulation of protein synthesis by phosphorylation of translation initiation factor eIF2. Phosphorylation results in low availability of the eIF2 ternary complex (eIF2-GTP-tRNAi) by affecting the interaction of eIF2 with its GTP-GDP exchange factor eIF2B. We have determined the cryo-EM structure of yeast eIF2B in complex with phosphorylated eIF2 at an overall resolution of 4.2 Å. Two eIF2 molecules bind opposite sides of an eIF2B hetero-decamer through eIF2α-D1, which contains the phosphorylated Ser51. eIF2α-D1 is mainly inserted between the N-terminal helix bundle domains of δ and α subunits of eIF2B. Phosphorylation of Ser51 enhances binding to eIF2B through direct interactions of phosphate groups with residues in eIF2Bα and indirectly by inducing contacts of eIF2α helix 58-63 with eIF2Bδ leading to a competition with Met-tRNAi.

Articles - 6qg6 mentioned but not cited (1)

  1. VESPER: global and local cryo-EM map alignment using local density vectors. Han X, Terashi G, Christoffer C, Chen S, Kihara D. Nat Commun 12 2090 (2021)


Reviews citing this publication (13)

  1. The integrated stress response: From mechanism to disease. Costa-Mattioli M, Walter P. Science 368 eaat5314 (2020)
  2. A guide to understanding endoplasmic reticulum stress in metabolic disorders. Lemmer IL, Willemsen N, Hilal N, Bartelt A. Mol Metab 47 101169 (2021)
  3. Nonsense-mediated RNA decay and its bipolar function in cancer. Nogueira G, Fernandes R, García-Moreno JF, Romão L. Mol Cancer 20 72 (2021)
  4. Pharmacological targeting of endoplasmic reticulum stress in disease. Marciniak SJ, Chambers JE, Ron D. Nat Rev Drug Discov 21 115-140 (2022)
  5. Pharmacological Manipulation of Translation as a Therapeutic Target for Chronic Pain. Yousuf MS, Shiers SI, Sahn JJ, Price TJ. Pharmacol Rev 73 59-88 (2021)
  6. Review: Emerging roles of the signaling network of the protein kinase GCN2 in the plant stress response. Lokdarshi A, von Arnim AG. Plant Sci 320 111280 (2022)
  7. Surviving and Adapting to Stress: Translational Control and the Integrated Stress Response. Wek RC, Anthony TG, Staschke KA. Antioxid Redox Signal 39 351-373 (2023)
  8. Regulation and function of elF2B in neurological and metabolic disorders. Hanson FM, Hodgson RE, de Oliveira MIR, Allen KE, Campbell SG. Biosci Rep 42 BSR20211699 (2022)
  9. A stay of execution: ATF4 regulation and potential outcomes for the integrated stress response. Neill G, Masson GR. Front Mol Neurosci 16 1112253 (2023)
  10. Move and countermove: the integrated stress response in picorna- and coronavirus-infected cells. Aloise C, Schipper JG, de Groot RJ, van Kuppeveld FJ. Curr Opin Immunol 79 102254 (2022)
  11. Protein Kinase R in Bacterial Infections: Friend or Foe? Smyth R, Sun J. Front Immunol 12 702142 (2021)
  12. Role of Cyclin-Dependent Kinase 1 in Translational Regulation in the M-Phase. Kalous J, Jansová D, Šušor A. Cells 9 (2020)
  13. The molecular basis of translation initiation and its regulation in eukaryotes. Brito Querido J, Díaz-López I, Ramakrishnan V. Nat Rev Mol Cell Biol (2023)

Articles citing this publication (21)

  1. eIF2B conformation and assembly state regulate the integrated stress response. Schoof M, Boone M, Wang L, Lawrence R, Frost A, Walter P. Elife 10 e65703 (2021)
  2. eIF2B and the Integrated Stress Response: A Structural and Mechanistic View. Marintchev A, Ito T. Biochemistry 59 1299-1308 (2020)
  3. Reorganization of budding yeast cytoplasm upon energy depletion. Marini G, Nüske E, Leng W, Alberti S, Pigino G. Mol Biol Cell 31 1232-1245 (2020)
  4. Sugar phosphate activation of the stress sensor eIF2B. Hao Q, Heo JM, Nocek BP, Hicks KG, Stoll VS, Remarcik C, Hackett S, LeBon L, Jain R, Eaton D, Rutter J, Wong YL, Sidrauski C. Nat Commun 12 3440 (2021)
  5. A point mutation in the nucleotide exchange factor eIF2B constitutively activates the integrated stress response by allosteric modulation. Boone M, Wang L, Lawrence RE, Frost A, Walter P, Schoof M. Elife 11 e76171 (2022)
  6. Mutational analysis of the alpha subunit of eIF2B provides insights into the role of eIF2B bodies in translational control and VWM disease. Norris K, Hodgson RE, Dornelles T, Allen KE, Abell BM, Ashe MP, Campbell SG. J Biol Chem 296 100207 (2021)
  7. An immunogenic cell injury module for the single-cell multiplexed activity metabolomics platform to identify promising anti-cancer natural products. Balsamo JA, Penton KE, Zhao Z, Hayes MJ, Lima SM, Irish JM, Bachmann BO. J Biol Chem 298 102300 (2022)
  8. Characterization of the Putative Acylated Cellulose Synthase Operon in Komagataeibacter xylinus E25. Szymczak I, Pietrzyk-Brzezińska AJ, Duszyński K, Ryngajłło M. Int J Mol Sci 23 7851 (2022)
  9. Elucidation of the Translation Initiation Factor Interaction Network of Haloferax volcanii Reveals Coupling of Transcription and Translation in Haloarchaea. Schramm F, Borst A, Linne U, Soppa J. Front Microbiol 12 742806 (2021)
  10. Fluorescence Intensity-Based eIF2B's Guanine Nucleotide-Exchange Factor Activity Assay. Sekine Y, Ron D, Zyryanova AF. Methods Mol Biol 2428 187-196 (2022)
  11. GTP binding to translation factor eIF2B stimulates its guanine nucleotide exchange activity. Kershaw CJ, Jennings MD, Cortopassi F, Guaita M, Al-Ghafli H, Pavitt GD. iScience 24 103454 (2021)
  12. ISRIB Blunts the Integrated Stress Response by Allosterically Antagonising the Inhibitory Effect of Phosphorylated eIF2 on eIF2B. Zyryanova AF, Kashiwagi K, Rato C, Harding HP, Crespillo-Casado A, Perera LA, Sakamoto A, Nishimoto M, Yonemochi M, Shirouzu M, Ito T, Ron D. Mol Cell 81 88-103.e6 (2021)
  13. Inhibition of Nonsense-Mediated Decay Induces Nociceptive Sensitization through Activation of the Integrated Stress Response. de la Peña JB, Chase R, Kunder N, Smith PR, Lou TF, Stanowick A, Suresh P, Shukla T, Butcher SE, Price TJ, Campbell ZT. J Neurosci 43 2921-2933 (2023)
  14. Inhibition of protein translation under matrix-deprivation stress in breast cancer cells. Warrier S, Srinivasan S, Chedere A, Rangarajan A. Front Med (Lausanne) 10 1124514 (2023)
  15. Newly synthesized mRNA escapes translational repression during the acute phase of the mammalian unfolded protein response. Alzahrani MR, Guan BJ, Zagore LL, Wu J, Chen CW, Licatalosi DD, Baker KE, Hatzoglou M. PLoS One 17 e0271695 (2022)
  16. Perspective: Modulating the integrated stress response to slow aging and ameliorate age-related pathology. Derisbourg MJ, Hartman MD, Denzel MS. Nat Aging 1 760-768 (2021)
  17. Stepwise assembly of the eukaryotic translation initiation factor 2 complex. Vanselow S, Neumann-Arnold L, Wojciech-Moock F, Seufert W. J Biol Chem 298 101583 (2022)
  18. The Integrated Stress Response Is Tumorigenic and Constitutes a Therapeutic Liability in Somatotroph Adenomas. Li Z, Chen Y, Yao X, Liu Q, Zhu H, Zhang Y, Feng J, Gao H. Int J Mol Sci 23 13067 (2022)
  19. Viral evasion of the integrated stress response through antagonism of eIF2-P binding to eIF2B. Schoof M, Wang L, Cogan JZ, Lawrence RE, Boone M, Wuerth JD, Frost A, Walter P. Nat Commun 12 7103 (2021)
  20. eIF2B as a Target for Viral Evasion of PKR-Mediated Translation Inhibition. Wuerth JD, Habjan M, Kainulainen M, Berisha B, Bertheloot D, Superti-Furga G, Pichlmair A, Weber F. mBio 11 (2020)
  21. eIF2Bδ blocks the integrated stress response and maintains eIF2B activity and cancer metastasis by overexpression in breast cancer stem cells. Gupta M, Walters BA, Katsara O, Granados Blanco K, Geter PA, Schneider RJ. Proc Natl Acad Sci U S A 120 e2207898120 (2023)


Quick links