EMDB/PDB/SASBDBから引用されている文献のデータベース

キーワード
構造解析手法	All X線回折 NMR 電子顕微鏡小角散乱中性子線回折線維回折粉末回折赤外分光 EPR FRET 理論モデルハイブリッド
著者・登録者
ジャーナル
IF	>30 >20 >10 >5 all

タイトル	The molecular basis of tRNA selectivity by human pseudouridine synthase 3.
ジャーナル・号・ページ	Mol Cell, Vol. 84, Issue 13, Page 2472-22489.e8, Year 2024
掲載日	2024年7月11日
著者	Ting-Yu Lin / Leon Kleemann / Jakub Jeżowski / Dominika Dobosz / Michał Rawski / Paulina Indyka / Grzegorz Ważny / Rahul Mehta / Andrzej Chramiec-Głąbik / Łukasz Koziej / Tristan Ranff / Christian Fufezan / Mateusz Wawro / Jakub Kochan / Joanna Bereta / Sebastian A Leidel / Sebastian Glatt /
PubMed 要旨	Pseudouridine (Ψ), the isomer of uridine, is ubiquitously found in RNA, including tRNA, rRNA, and mRNA. Human pseudouridine synthase 3 (PUS3) catalyzes pseudouridylation of position 38/39 in tRNAs. ...Pseudouridine (Ψ), the isomer of uridine, is ubiquitously found in RNA, including tRNA, rRNA, and mRNA. Human pseudouridine synthase 3 (PUS3) catalyzes pseudouridylation of position 38/39 in tRNAs. However, the molecular mechanisms by which it recognizes its RNA targets and achieves site specificity remain elusive. Here, we determine single-particle cryo-EM structures of PUS3 in its apo form and bound to three tRNAs, showing how the symmetric PUS3 homodimer recognizes tRNAs and positions the target uridine next to its active site. Structure-guided and patient-derived mutations validate our structural findings in complementary biochemical assays. Furthermore, we deleted PUS1 and PUS3 in HEK293 cells and mapped transcriptome-wide Ψ sites by Pseudo-seq. Although PUS1-dependent sites were detectable in tRNA and mRNA, we found no evidence that human PUS3 modifies mRNAs. Our work provides the molecular basis for PUS3-mediated tRNA modification in humans and explains how its tRNA modification activity is linked to intellectual disabilities.
リンク	Mol Cell / PubMed:38996458 / PubMed Central
手法	EM (単粒子)
解像度	2.66 - 6.5 Å
構造データ	16917 9f9q EMDB-16917: Human apo pseudouridine synthase 3 (PUS3) PDB-9f9q: Human apo pseudouridine synthase 3 (PUS3 D118A mutant) 手法: EM (単粒子) / 解像度: 6.5 Å 16926 8okd EMDB-16926, PDB-8okd: Human pseudouridine synthase 3 and tRNA-Gln 手法: EM (単粒子) / 解像度: 3.1 Å 19830 9enb EMDB-19830, PDB-9enb: Human pseudouridine synthase 3 (PUS3 R116A mutant) and two tRNA-Gln 手法: EM (単粒子) / 解像度: 2.66 Å 19831 9enc EMDB-19831, PDB-9enc: Human pseudouridine synthase 3 (PUS3 R116A mutant) and one tRNA-Gln 手法: EM (単粒子) / 解像度: 3.36 Å 19832 9ene EMDB-19832, PDB-9ene: Human pseudouridine synthase 3 (PUS3 D118A mutant) and two tRNA-Arg 手法: EM (単粒子) / 解像度: 3.15 Å 19833 9enf EMDB-19833, PDB-9enf: Human pseudouridine synthase 3 (PUS3 D118A mutant) and two pre-tRNA-Arg 手法: EM (単粒子) / 解像度: 2.97 Å EMDB-19834: Human pseudouridine synthase 3 (PUS3 R116A mutant) 手法: EM (単粒子) / 解像度: 4.49 Å EMDB-19835: Human pseudouridine synthase 3 (PUS3 K119A mutant) 手法: EM (単粒子) / 解像度: 5.15 Å EMDB-19836: Human pseudouridine synthase 3 (wild type) 手法: EM (単粒子) / 解像度: 4.02 Å
化合物	ChemComp-MG: Unknown entry / マグネシウムジカチオン
由来	homo sapiens (ヒト)
キーワード	RNA BINDING PROTEIN / RNA modification / pseudouridylation / tRNA / homodimer