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Structure-function analysis of Sua5 protein reveals novel functional motifs required for the biosynthesis of the universal t6A tRNA modification.

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Pichard-Kostuch A, Zhang W, Liger D, Daugeron MC, Létoquart J, Li de la Sierra-Gallay I, Forterre P, Collinet B, van Tilbeurgh H, Basta T
OpenAccess logo RNA 24 926-938 (2018)
Related entries: 6f89, 6f8y

Cited: 10 times
EuropePMC logo PMID: 29650678

Abstract

N6-threonyl-carbamoyl adenosine (t6A) is a universal tRNA modification found at position 37, next to the anticodon, in almost all tRNAs decoding ANN codons (where N = A, U, G, or C). t6A stabilizes the codon-anticodon interaction and hence promotes translation fidelity. The first step of the biosynthesis of t6A, the production of threonyl-carbamoyl adenylate (TC-AMP), is catalyzed by the Sua5/TsaC family of enzymes. While TsaC is a single domain protein, Sua5 enzymes are composed of the TsaC-like domain, a linker and an extra domain called SUA5 of unknown function. In the present study, we report structure-function analysis of Pyrococcus abyssi Sua5 (Pa-Sua5). Crystallographic data revealed binding sites for bicarbonate substrate and pyrophosphate product. The linker of Pa-Sua5 forms a loop structure that folds into the active site gorge and closes it. Using structure-guided mutational analysis, we established that the conserved sequence motifs in the linker and the domain-domain interface are essential for the function of Pa-Sua5. We propose that the linker participates actively in the biosynthesis of TC-AMP by binding to ATP/PPi and by stabilizing the N-carboxy-l-threonine intermediate. Hence, TsaC orthologs which lack such a linker and SUA5 domain use a different mechanism for TC-AMP synthesis.

Articles - 6f87 mentioned but not cited (4)

  1. Structure-function analysis of Sua5 protein reveals novel functional motifs required for the biosynthesis of the universal t6A tRNA modification. Pichard-Kostuch A, Zhang W, Liger D, Daugeron MC, Létoquart J, Li de la Sierra-Gallay I, Forterre P, Collinet B, van Tilbeurgh H, Basta T. RNA 24 926-938 (2018)
  2. Complex fitness landscape shapes variation in a hyperpolymorphic species. Stolyarova AV, Neretina TV, Zvyagina EA, Fedotova AV, Kondrashov AS, Bazykin GA. Elife 11 e76073 (2022)
  3. Structure-function analysis of an ancient TsaD-TsaC-SUA5-TcdA modular enzyme reveals a prototype of tRNA t6A and ct6A synthetases. Jin M, Zhang Z, Yu Z, Chen W, Wang X, Lei D, Zhang W. Nucleic Acids Res 51 8711-8729 (2023)
  4. The universal Sua5/TsaC family evolved different mechanisms for the synthesis of a key tRNA modification. Pichard-Kostuch A, Da Cunha V, Oberto J, Sauguet L, Basta T. Front Microbiol 14 1204045 (2023)


Reviews citing this publication (3)

  1. Transfer RNA Modification Enzymes from Thermophiles and Their Modified Nucleosides in tRNA. Hori H, Kawamura T, Awai T, Ochi A, Yamagami R, Tomikawa C, Hirata A. Microorganisms 6 E110 (2018)
  2. The structural and functional workings of KEOPS. Beenstock J, Sicheri F. Nucleic Acids Res 49 10818-10834 (2021)
  3. Conservation and Diversification of tRNA t6A-Modifying Enzymes across the Three Domains of Life. Su C, Jin M, Zhang W. Int J Mol Sci 23 13600 (2022)

Articles citing this publication (3)

  1. Defects in t6A tRNA modification due to GON7 and YRDC mutations lead to Galloway-Mowat syndrome. Arrondel C, Missoury S, Snoek R, Patat J, Menara G, Collinet B, Liger D, Durand D, Gribouval O, Boyer O, Buscara L, Martin G, Machuca E, Nevo F, Lescop E, Braun DA, Boschat AC, Sanquer S, Guerrera IC, Revy P, Parisot M, Masson C, Boddaert N, Charbit M, Decramer S, Novo R, Macher MA, Ranchin B, Bacchetta J, Laurent A, Collardeau-Frachon S, van Eerde AM, Hildebrandt F, Magen D, Antignac C, van Tilbeurgh H, Mollet G. Nat Commun 10 3967 (2019)
  2. Structure of a reaction intermediate mimic in t6A biosynthesis bound in the active site of the TsaBD heterodimer from Escherichia coli. Kopina BJ, Missoury S, Collinet B, Fulton MG, Cirio C, van Tilbeurgh H, Lauhon CT. Nucleic Acids Res 49 2141-2160 (2021)
  3. New biochemistry in the Rhodanese-phosphatase superfamily: emerging roles in diverse metabolic processes, nucleic acid modifications, and biological conflicts. Burroughs AM, Aravind L. NAR Genom Bioinform 5 lqad029 (2023)


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