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

被引：7

作者：

Sievers, Katharina ^{[1
]}

Neumann, Piotr ^{[1
]}

Susac, Lukas ^{[2
]}

Da Vela, Stefano ^{[3
]}

Graewert, Melissa ^{[3
]}

Trowitzsch, Simon ^{[2
]}

Svergun, Dmitri ^{[3
,5
]}

Tampe, Robert ^{[2
]}

Ficner, Ralf ^{[1
,4
]}

机构：

[1] Univ Gottingen, Dept Mol Struct Biol, GZMB, D-37077 Gottingen, Germany

[2] Goethe Univ Frankfurt, Inst Biochem, Bioctr, D-60438 Frankfurt, Germany

[3] EMBL DESY, European Mol Biol Lab, Hamburg Outstat, D-22607 Hamburg, Germany

[4] Univ Gottingen, Mol Machines Networks Excitable Cells MBExC, Cluster Excellence Multiscale Bioimaging, D-37075 Gottingen, Germany

[5] BIOSAXS GmbH, D-22607 Hamburg, Germany

来源：

STRUCTURE | 2024年 / 32卷 / 03期

关键词：

ESCHERICHIA-COLI; CRYSTAL-STRUCTURE; S-ADENOSYLMETHIONINE; SHIGELLA-FLEXNERI; NUCLEOSIDE-Q; KINETIC MECHANISM; QUEUOSINE; QUEUINE; EPOXYQUEUOSINE; PROTEIN;

D O I：

10.1016/j.str.2023.12.006

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：316 / 327.e5

页数：18

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