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The Elongator subunit Elp3 is a non-canonical tRNA acetyltransferase.

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Lin TY, Abbassi NEH, Zakrzewski K, Chramiec-Głąbik A, Jemioła-Rzemińska M, Różycki J, Glatt S
OpenAccess logo Nat Commun 10 625 (2019)
Related entries: 6ia8, 6iad, 6iaz

Cited: 35 times
EuropePMC logo PMID: 30733442

Abstract

The Elongator complex catalyzes posttranscriptional tRNA modifications by attaching carboxy-methyl (cm5) moieties to uridine bases located in the wobble position. The catalytic subunit Elp3 is highly conserved and harbors two individual subdomains, a radical S-adenosyl methionine (rSAM) and a lysine acetyltransferase (KAT) domain. The details of its modification reaction cycle and particularly the substrate specificity of its KAT domain remain elusive. Here, we present the co-crystal structure of bacterial Elp3 (DmcElp3) bound to an acetyl-CoA analog and compare it to the structure of a monomeric archaeal Elp3 from Methanocaldococcus infernus (MinElp3). Furthermore, we identify crucial active site residues, confirm the importance of the extended N-terminus for substrate recognition and uncover the specific induction of acetyl-CoA hydrolysis by different tRNA species. In summary, our results establish the clinically relevant Elongator subunit as a non-canonical acetyltransferase and genuine tRNA modification enzyme.

Reviews - 6ia6 mentioned but not cited (1)

  1. How Elongator Acetylates tRNA Bases. Abbassi NE, Biela A, Glatt S, Lin TY. Int J Mol Sci 21 E8209 (2020)

Articles - 6ia6 mentioned but not cited (1)

  1. The Elongator subunit Elp3 is a non-canonical tRNA acetyltransferase. Lin TY, Abbassi NEH, Zakrzewski K, Chramiec-Głąbik A, Jemioła-Rzemińska M, Różycki J, Glatt S. Nat Commun 10 625 (2019)


Reviews citing this publication (7)

  1. Iron-sulfur clusters as inhibitors and catalysts of viral replication. Honarmand Ebrahimi K, Ciofi-Baffoni S, Hagedoorn PL, Nicolet Y, Le Brun NE, Hagen WR, Armstrong FA. Nat Chem 14 253-266 (2022)
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  3. Anticodon Wobble Uridine Modification by Elongator at the Crossroad of Cell Signaling, Differentiation, and Diseases. Hermand D. Epigenomes 4 7 (2020)
  4. Plant Elongator-Protein Complex of Diverse Activities Regulates Growth, Development, and Immune Responses. Jarosz M, Van Lijsebettens M, Woloszynska M. Int J Mol Sci 21 E6912 (2020)
  5. The diverse structural modes of tRNA binding and recognition. Biela A, Hammermeister A, Kaczmarczyk I, Walczak M, Koziej L, Lin TY, Glatt S. J Biol Chem 299 104966 (2023)
  6. Highlighting the Unique Roles of Radical S-Adenosylmethionine Enzymes in Methanogenic Archaea. Boswinkle K, McKinney J, Allen KD. J Bacteriol 204 e0019722 (2022)
  7. "Superwobbling" and tRNA-34 Wobble and tRNA-37 Anticodon Loop Modifications in Evolution and Devolution of the Genetic Code. Lei L, Burton ZF. Life (Basel) 12 252 (2022)

Articles citing this publication (26)

  1. Molecular basis of tRNA recognition by the Elongator complex. Dauden MI, Jaciuk M, Weis F, Lin TY, Kleindienst C, Abbassi NEH, Khatter H, Krutyhołowa R, Breunig KD, Kosinski J, Müller CW, Glatt S. Sci Adv 5 eaaw2326 (2019)
  2. The novel PII-interactor PirC identifies phosphoglycerate mutase as key control point of carbon storage metabolism in cyanobacteria. Orthwein T, Scholl J, Spät P, Lucius S, Koch M, Macek B, Hagemann M, Forchhammer K. Proc Natl Acad Sci U S A 118 e2019988118 (2021)
  3. Elp2 mutations perturb the epitranscriptome and lead to a complex neurodevelopmental phenotype. Kojic M, Gawda T, Gaik M, Begg A, Salerno-Kochan A, Kurniawan ND, Jones A, Drożdżyk K, Kościelniak A, Chramiec-Głąbik A, Hediyeh-Zadeh S, Kasherman M, Shim WJ, Sinniah E, Genovesi LA, Abrahamsen RK, Fenger CD, Madsen CG, Cohen JS, Fatemi A, Stark Z, Lunke S, Lee J, Hansen JK, Boxill MF, Keren B, Marey I, Saenz MS, Brown K, Alexander SA, Mureev S, Batzilla A, Davis MJ, Piper M, Bodén M, Burne THJ, Palpant NJ, Møller RS, Glatt S, Wainwright BJ. Nat Commun 12 2678 (2021)
  4. A Systems Chemoproteomic Analysis of Acyl-CoA/Protein Interaction Networks. Levy MJ, Montgomery DC, Sardiu ME, Montano JL, Bergholtz SE, Nance KD, Thorpe AL, Fox SD, Lin Q, Andresson T, Florens L, Washburn MP, Meier JL. Cell Chem Biol 27 322-333.e5 (2020)
  5. Functional divergence of the two Elongator subcomplexes during neurodevelopment. Gaik M, Kojic M, Stegeman MR, Öncü-Öner T, Kościelniak A, Jones A, Mohamed A, Chau PYS, Sharmin S, Chramiec-Głąbik A, Indyka P, Rawski M, Biela A, Dobosz D, Millar A, Chau V, Ünalp A, Piper M, Bellingham MC, Eichler EE, Nickerson DA, Güleryüz H, Abbassi NEH, Jazgar K, Davis MJ, Mercimek-Andrews S, Cingöz S, Wainwright BJ, Glatt S. EMBO Mol Med 14 e15608 (2022)
  6. Loss of Elongator- and KEOPS-Dependent tRNA Modifications Leads to Severe Growth Phenotypes and Protein Aggregation in Yeast. Pollo-Oliveira L, Klassen R, Davis N, Ciftci A, Bacusmo JM, Martinelli M, DeMott MS, Begley TJ, Dedon PC, Schaffrath R, de Crécy-Lagard V. Biomolecules 10 E322 (2020)
  7. Molecular basis for the bifunctional Uba4-Urm1 sulfur-relay system in tRNA thiolation and ubiquitin-like conjugation. Pabis M, Termathe M, Ravichandran KE, Kienast SD, Krutyhołowa R, Sokołowski M, Jankowska U, Grudnik P, Leidel SA, Glatt S. EMBO J 39 e105087 (2020)
  8. ATP-citrate lyase promotes axonal transport across species. Even A, Morelli G, Turchetto S, Shilian M, Bail RL, Laguesse S, Krusy N, Brisker A, Brandis A, Inbar S, Chariot A, Saudou F, Dietrich P, Dragatsis I, Brone B, Broix L, Rigo JM, Weil M, Nguyen L. Nat Commun 12 5878 (2021)
  9. Serum Circ-FAF1/Circ-ELP3: A novel potential biomarker for breast cancer diagnosis. Omid-Shafaat R, Moayeri H, Rahimi K, Menbari MN, Vahabzadeh Z, Hakhamaneshi MS, Nouri B, Ghaderi B, Abdi M. J Clin Lab Anal 35 e24008 (2021)
  10. Destabilization of mutated human PUS3 protein causes intellectual disability. Lin TY, Smigiel R, Kuzniewska B, Chmielewska JJ, Kosińska J, Biela M, Biela A, Kościelniak A, Dobosz D, Laczmanska I, Chramiec-Głąbik A, Jeżowski J, Nowak J, Gos M, Rzonca-Niewczas S, Dziembowska M, Ploski R, Glatt S. Hum Mutat 43 2063-2078 (2022)
  11. Cryo-EM structure of the fully assembled Elongator complex. Jaciuk M, Scherf D, Kaszuba K, Gaik M, Rau A, Kościelniak A, Krutyhołowa R, Rawski M, Indyka P, Graziadei A, Chramiec-Głąbik A, Biela A, Dobosz D, Lin TY, Abbassi NE, Hammermeister A, Rappsilber J, Kosinski J, Schaffrath R, Glatt S. Nucleic Acids Res 51 2011-2032 (2023)
  12. A novel ELP1 mutation impairs the function of the Elongator complex and causes a severe neurodevelopmental phenotype. Kojic M, Abbassi NEH, Lin TY, Jones A, Wakeling EL, Clement E, Nakou V, Singleton M, Dobosz D, Kaliakatsos M, Glatt S, Wainwright BJ. J Hum Genet 68 445-453 (2023)
  13. Aspergillus fumigatus Elongator complex subunit 3 affects hyphal growth, adhesion and virulence through wobble uridine tRNA modification. Zhang Y, Wang Y, Fan J, Zhu G, Lu L. PLoS Pathog 18 e1010976 (2022)
  14. Elongator stabilizes microtubules to control central spindle asymmetry and polarized trafficking of cell fate determinants. Planelles-Herrero VJ, Bittleston A, Seum C, Daeden A, Gaitan MG, Derivery E. Nat Cell Biol 24 1606-1616 (2022)
  15. Fungal Kti12 proteins display unusual linker regions and unique ATPase p-loops. Krutyhołowa R, Reinhardt-Tews A, Chramiec-Głąbik A, Breunig KD, Glatt S. Curr Genet 66 823-833 (2020)
  16. Global Histone H3 Lysine 4 Trimethylation (H3K4me3) Landscape Changes in Response to TGFβ. Naik A, Dalpatraj N, Thakur N. Epigenet Insights 14 25168657211051755 (2021)
  17. Loss of Elp1 perturbs histone H2A.Z and the Notch signaling pathway. Cameron B, Lehrmann E, Chih T, Walters J, Buksch R, Snyder S, Goffena J, Lefcort F, Becker KG, George L. Biol Open 10 bio058979 (2021)
  18. Biochemical and Structural Characterization of Human Core Elongator and Its Subassemblies. Dalwadi U, Mannar D, Zierhut F, Yip CK. ACS Omega 7 3424-3433 (2022)
  19. Elongator Subunit 3 (Elp3) Is Required for Zebrafish Trunk Development. Rojas-Benítez D, Allende ML. Int J Mol Sci 21 E925 (2020)
  20. A novel splice variant of Elp3/Kat9 regulates mitochondrial tRNA modification and function. Boutoual R, Jo H, Heckenbach I, Tiwari R, Kasler H, Lerner CA, Shah S, Schilling B, Calvanese V, Rardin MJ, Scheibye-Knudsen M, Verdin E. Sci Rep 12 14804 (2022)
  21. AtELP4 a subunit of the Elongator complex in Arabidopsis, mediates cell proliferation and dorsoventral polarity during leaf morphogenesis. Jun SE, Cho KH, Manzoor MA, Hwang TY, Kim YS, Schaffrath R, Kim GT. Front Plant Sci 13 1033358 (2022)
  22. Computational engineering of previously crystallized pyruvate formate-lyase activating enzyme reveals insights into SAM binding and reductive cleavage. Moody JD, Hill S, Lundahl MN, Saxton AJ, Galambas A, Broderick WE, Lawrence CM, Broderick JB. J Biol Chem 299 104791 (2023)
  23. Electrophoretic Mobility Shift Assay (EMSA) and Microscale Thermophoresis (MST) Methods to Measure Interactions Between tRNAs and Their Modifying Enzymes. Chramiec-Głąbik A, Rawski M, Glatt S, Lin TY. Methods Mol Biol 2666 29-53 (2023)
  24. Proteomic Analysis of Methanococcus voltae Grown in the Presence of Mineral and Nonmineral Sources of Iron and Sulfur. Steward KF, Payne D, Kincannon W, Johnson C, Lensing M, Fausset H, Németh B, Shepard EM, Broderick WE, Broderick JB, Dubois J, Bothner B. Microbiol Spectr 10 e0189322 (2022)
  25. Transcriptome analysis in a humanized mouse model of familial dysautonomia reveals tissue-specific gene expression disruption in the peripheral nervous system. Harripaul R, Morini E, Salani M, Logan E, Kirchner E, Bolduc J, Chekuri A, Currall B, Yadav R, Erdin S, Talkowski ME, Gao D, Slaugenhaupt S. Sci Rep 14 570 (2024)
  26. Yeast gene KTI13 (alias DPH8) operates in the initiation step of diphthamide synthesis on elongation factor 2. Arend M, Ütkür K, Hawer H, Mayer K, Ranjan N, Adrian L, Brinkmann U, Schaffrath R. Microb Cell 10 195-203 (2023)


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