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Structural basis of specific tRNA aminoacylation by a small in vitro selected ribozyme.

Xiao H, Murakami H, Suga H, Ferré-D'Amaré AR
Nature 454 358-61 (2008)
Cited: 87 times
EuropePMC logo PMID: 18548004

Abstract

In modern organisms, protein enzymes are solely responsible for the aminoacylation of transfer RNA. However, the evolution of protein synthesis in the RNA world required RNAs capable of catalysing this reaction. Ribozymes that aminoacylate RNA by using activated amino acids have been discovered through selection in vitro. Flexizyme is a 45-nucleotide ribozyme capable of charging tRNA in trans with various activated l-phenylalanine derivatives. In addition to a more than 10(5) rate enhancement and more than 10(4)-fold discrimination against some non-cognate amino acids, this ribozyme achieves good regioselectivity: of all the hydroxyl groups of a tRNA, it exclusively aminoacylates the terminal 3'-OH. Here we report the 2.8-A resolution structure of flexizyme fused to a substrate RNA. Together with randomization of ribozyme core residues and reselection, this structure shows that very few nucleotides are needed for the aminoacylation of specific tRNAs. Although it primarily recognizes tRNA through base-pairing with the CCA terminus of the tRNA molecule, flexizyme makes numerous local interactions to position the acceptor end of tRNA precisely. A comparison of two crystallographically independent flexizyme conformations, only one of which appears capable of binding activated phenylalanine, suggests that this ribozyme may achieve enhanced specificity by coupling active-site folding to tRNA docking. Such a mechanism would be reminiscent of the mutually induced fit of tRNA and protein employed by some aminoacyl-tRNA synthetases to increase specificity.

Reviews - 3cul mentioned but not cited (1)

  1. Use of the spliceosomal protein U1A to facilitate crystallization and structure determination of complex RNAs. Ferré-D'Amaré AR. Methods 52 159-167 (2010)

Articles - 3cul mentioned but not cited (5)



Reviews citing this publication (27)

  1. Riboswitches: discovery of drugs that target bacterial gene-regulatory RNAs. Deigan KE, Ferré-D'Amaré AR. Acc Chem Res 44 1329-1338 (2011)
  2. Ribozymes and riboswitches: modulation of RNA function by small molecules. Zhang J, Lau MW, Ferré-D'Amaré AR. Biochemistry 49 9123-9131 (2010)
  3. A RaPID way to discover nonstandard macrocyclic peptide modulators of drug targets. Passioura T, Suga H. Chem Commun (Camb) 53 1931-1940 (2017)
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  7. The glmS ribozyme: use of a small molecule coenzyme by a gene-regulatory RNA. Ferré-D'Amaré AR. Q Rev Biophys 43 423-447 (2010)
  8. Structure and mechanism of the T-box riboswitches. Zhang J, Ferré-D'Amaré AR. Wiley Interdiscip Rev RNA 6 419-433 (2015)
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  10. New molecular engineering approaches for crystallographic studies of large RNAs. Zhang J, Ferré-D'Amaré AR. Curr Opin Struct Biol 26 9-15 (2014)
  11. Technologies for the synthesis of mRNA-encoding libraries and discovery of bioactive natural product-inspired non-traditional macrocyclic peptides. Ito K, Passioura T, Suga H. Molecules 18 3502-3528 (2013)
  12. Selenium derivatization of nucleic acids for X-ray crystal-structure and function studies. Sheng J, Huang Z. Chem Biodivers 7 753-785 (2010)
  13. Unboxing the T-box riboswitches-A glimpse into multivalent and multimodal RNA-RNA interactions. Zhang J. Wiley Interdiscip Rev RNA 11 e1600 (2020)
  14. Recent developments of engineered translational machineries for the incorporation of non-canonical amino acids into polypeptides. Terasaka N, Iwane Y, Geiermann AS, Goto Y, Suga H. Int J Mol Sci 16 6513-6531 (2015)
  15. Progress in synthesizing protocells. Toparlak OD, Mansy SS. Exp Biol Med (Maywood) 244 304-313 (2019)
  16. Beyond mRNA: The role of non-coding RNAs in normal and aberrant hematopoiesis. Wilkes MC, Repellin CE, Sakamoto KM. Mol Genet Metab 122 28-38 (2017)
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  18. Emerging Methods for Efficient and Extensive Incorporation of Non-canonical Amino Acids Using Cell-Free Systems. Wu Y, Wang Z, Qiao X, Li J, Shu X, Qi H. Front Bioeng Biotechnol 8 863 (2020)
  19. Recent Advances Toward the Discovery of Drug-Like Peptides De novo. Goldflam M, Ullman CG. Front Chem 3 69 (2015)
  20. General Strategies for RNA X-ray Crystallography. Jackson RW, Smathers CM, Robart AR. Molecules 28 2111 (2023)
  21. Biochemistry of Aminoacyl tRNA Synthetase and tRNAs and Their Engineering for Cell-Free and Synthetic Cell Applications. Ganesh RB, Maerkl SJ. Front Bioeng Biotechnol 10 918659 (2022)
  22. In Vitro Selection Combined with Ribosomal Translation Containing Non-proteinogenic Amino Acids. Fujino T, Murakami H. Chem Rec 16 365-377 (2016)
  23. Cell-free Biosynthesis of Peptidomimetics. Lee K, Willi JA, Cho N, Kim I, Jewett MC, Lee J. Biotechnol Bioprocess Eng 1-17 (2023)
  24. Base Pairing Promoted the Self-Organization of Genetic Coding, Catalysis, and Free-Energy Transduction. Carter CW. Life (Basel) 14 199 (2024)
  25. Landmarks in the Evolution of (t)-RNAs from the Origin of Life up to Their Present Role in Human Cognition. Balke D, Kuss A, Müller S. Life (Basel) 6 E1 (2015)
  26. Noncanonical Amino Acids in Biocatalysis. Birch-Price Z, Hardy FJ, Lister TM, Kohn AR, Green AP. Chem Rev 124 8740-8786 (2024)
  27. Reprogramming the genetic code with flexizymes. Katoh T, Suga H. Nat Rev Chem (2024)

Articles citing this publication (54)



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