6I9R

Large subunit of the human mitochondrial ribosome in complex with Virginiamycin M and Quinupristin

これはPDB形式変換不可エントリーです。

6I9R の概要

• エントリーDOI: 10.2210/pdb6i9r/pdb
• EMDBエントリー: 4434
• 関連するBIRD辞書のPRD_ID: PRD_000505
• 分子名称: 39S ribosomal protein L32, mitochondrial, 39S ribosomal protein L41, mitochondrial, 16S rRNA, ... (56 entities in total)
• 機能のキーワード: ribosome, mitochondria
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 53
• 化学式量合計: 1745226.18

構造登録者

Modelska, A.,Aibara, S.,Amunts, A. (登録日: 2018-11-25, 公開日: 2020-07-08, 最終更新日: 2025-12-17)

主引用文献

Sighel, D.,Notarangelo, M.,Aibara, S.,Re, A.,Ricci, G.,Guida, M.,Soldano, A.,Adami, V.,Ambrosini, C.,Broso, F.,Rosatti, E.F.,Longhi, S.,Buccarelli, M.,D'Alessandris, Q.G.,Giannetti, S.,Pacioni, S.,Ricci-Vitiani, L.,Rorbach, J.,Pallini, R.,Roulland, S.,Amunts, A.,Mancini, I.,Modelska, A.,Quattrone, A.
Inhibition of mitochondrial translation suppresses glioblastoma stem cell growth.
Cell Rep, 35:109024-109024, 2021

PubMed Abstract: Glioblastoma stem cells (GSCs) resist current glioblastoma (GBM) therapies. GSCs rely highly on oxidative phosphorylation (OXPHOS), whose function requires mitochondrial translation. Here we explore the therapeutic potential of targeting mitochondrial translation and report the results of high-content screening with putative blockers of mitochondrial ribosomes. We identify the bacterial antibiotic quinupristin/dalfopristin (Q/D) as an effective suppressor of GSC growth. Q/D also decreases the clonogenicity of GSCs in vitro, consequently dysregulating the cell cycle and inducing apoptosis. Cryoelectron microscopy (cryo-EM) reveals that Q/D binds to the large mitoribosomal subunit, inhibiting mitochondrial protein synthesis and functionally dysregulating OXPHOS complexes. These data suggest that targeting mitochondrial translation could be explored to therapeutically suppress GSC growth in GBM and that Q/D could potentially be repurposed for cancer treatment.

PubMed: 33910005
DOI: 10.1016/j.celrep.2021.109024

実験手法

ELECTRON MICROSCOPY (3.9 Å)