Journal Article

PUBDB-2025-00183

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Structural and functional insights into tRNA recognition by human tRNA guanine transglycosylase

Sievers, K.Extern*EMBL* ; Neumann, P.Extern*EMBL* ; Sušac, L. ; Da Vela, S.Extern* ; Graewert, M.EMBL* ; Trowitzsch, S.Extern*EMBL* ; Svergun, D.EMBL* ; Tampé, R. ; Ficner, R. (Corresponding author)Extern*EMBL*

2024
Elsevier Science London [u.a.]

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Please use a persistent id in citations: 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.

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Contributing Institute(s):

1. DOOR-User (DOOR ; HAS-User)
2. EMBL (EMBL)

Research Program(s):

1. 6G3 - PETRA III (DESY) (POF4-6G3) (POF4-6G3)
2. DFG project G:(GEPRIS)390729940 - EXC 2067: Multiscale Bioimaging: Von molekularen Maschinen zu Netzwerken erregbarer Zellen (390729940) (390729940)
3. EditMHC - How MHC-I editing complexes shape the hierarchical immune response (789121) (789121)
4. SFB 860 Z01 - Zentrale Einrichtung für Kristallisationsexperimente (Z01) (174684579) (174684579)
5. SFB 860 A02 - Kristallographische Studien an molekularen Motoren des Spleißosoms (A02) (174570643) (174570643)
6. SFB 1565 P09 - Strukturelle und mechanistische Analyse des nukleozytoplasmatischen Transports von RNAs (P09) (515953039) (515953039)

Experiment(s):

1. PETRA Beamline P12 (PETRA III)

Appears in the scientific report 2024

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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