7YW2

Crystal structure of tRNA 2'-phosphotransferase from Mus musculus

7YW2 の概要

• エントリーDOI: 10.2210/pdb7yw2/pdb
• 分子名称: tRNA 2'-phosphotransferase 1, [[(2~{R},3~{S},4~{R},5~{R})-5-(6-aminopurin-9-yl)-3,4-bis(oxidanyl)oxolan-2-yl]methoxy-oxidanyl-phosphoryl] [(2~{R},3~{S},4~{R},5~{R})-3,4-bis(oxidanyl)-5-phosphonooxy-oxolan-2-yl]methyl hydrogen phosphate, GLYCEROL, ... (8 entities in total)
• 機能のキーワード: trna 2'-phosphotransferase, transferase
• 由来する生物種: Mus musculus (house mouse)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 29848.49

構造登録者

Yang, X.Y.,Liu, X.H. (登録日: 2022-08-21, 公開日: 2023-07-26, 最終更新日: 2026-03-04)

主引用文献

Yang, X.,Wang, J.,Li, S.,Li, X.,Gong, J.,Yan, Z.,Zhou, H.,Wu, C.,Liu, X.
Structural and biochemical insights into the molecular mechanism of TRPT1 for nucleic acid ADP-ribosylation.
Nucleic Acids Res., 51:7649-7665, 2023

PubMed Abstract: Nucleic acid ADP-ribosylation has been established as a novel modification found in a wide diversity of prokaryotic and eukaryotic organisms. tRNA 2'-phosphotransferase 1 (TRPT1/TPT1/KptA) possesses ADP-ribosyltransferase (ART) activity and is able to ADP-ribosylate nucleic acids. However, the underlying molecular mechanism remains elusive. Here, we determined crystal structures of TRPT1s in complex with NAD+ from Homo sapiens, Mus musculus and Saccharomyces cerevisiae. Our results revealed that the eukaryotic TRPT1s adopt common mechanisms for both NAD+ and nucleic acid substrate binding. The conserved SGR motif induces a significant conformational change in the donor loop upon NAD+ binding to facilitate the catalytic reaction of ART. Moreover, the nucleic acid-binding residue redundancy provides structural flexibility to accommodate different nucleic acid substrates. Mutational assays revealed that TRPT1s employ different catalytic and nucleic acid-binding residues to perform nucleic acid ADP-ribosylation and RNA 2'-phosphotransferase activities. Finally, cellular assays revealed that the mammalian TRPT1 is able to promote endocervical HeLa cell survival and proliferation. Together, our results provide structural and biochemical insights into the molecular mechanism of TRPT1 for nucleic acid ADP-ribosylation.

PubMed: 37334830
DOI: 10.1093/nar/gkad525

実験手法

X-RAY DIFFRACTION (2.23 Å)