2. Academic Validation
  3. Structural and functional insights into tRNA recognition by human tRNA guanine transglycosylase

Structural and functional insights into tRNA recognition by human tRNA guanine transglycosylase

  • Structure. 2023 Dec 27:S0969-2126(23)00447-1. doi: 10.1016/j.str.2023.12.006.
Katharina Sievers 1,  Piotr Neumann 1,  Lukas Sušac 2,  Stefano Da Vela 3,  Melissa Graewert 3,  Simon Trowitzsch 2,  Dmitri Svergun 3,  Robert Tampé 2,  Ralf Ficner 4
Affiliations

Affiliations

  • 1 Department of Molecular Structural Biology, GZMB, University of Göttingen, 37077 Göttingen, Germany.
  • 2 Institute of Biochemistry, Biocenter, Goethe University Frankfurt, 60438 Frankfurt/Main, Germany.
  • 3 European Molecular Biology Laboratory, Hamburg Outstation, EMBL c/o DESY, 22607 Hamburg, Germany.
  • 4 Department of Molecular Structural Biology, GZMB, University of Göttingen, 37077 Göttingen, Germany; Cluster of Excellence "Multiscale Bioimaging: From Molecular Machines to Networks of Excitable Cells" (MBExC), University of Göttingen, 37075 Göttingen, Germany. Electronic address: [email protected].
PMID: 38181786 DOI: 10.1016/j.str.2023.12.006
Abstract

Eukaryotic tRNA guanine transglycosylase (TGT) is an RNA-modifying Enzyme which catalyzes the base exchange of the genetically encoded guanine 34 of tRNAsAsp,Asn,His,Tyr for queuine, a hypermodified 7-deazaguanine derivative. Eukaryotic TGT is a heterodimer comprised of a catalytic and a non-catalytic subunit. While binding of the tRNA anticodon loop to the active site is structurally well understood, the contribution of the non-catalytic subunit to tRNA binding remained enigmatic, as no complex structure with a complete tRNA was available. Here, we report a cryo-EM structure of eukaryotic TGT in complex with a complete tRNA, revealing the crucial role of the non-catalytic subunit in tRNA binding. We decipher the functional significance of these additional tRNA-binding sites, analyze solution state conformation, flexibility, and disorder of apo TGT, and examine conformational transitions upon tRNA binding.

Keywords

RNA modification; RNA-binding; RNA-protein complex; nucleic acid binding; queuosine; single particle cryo-EM; small angle X-ray scattering.

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