6I9R
Large subunit of the human mitochondrial ribosome in complex with Virginiamycin M and Quinupristin
This is a non-PDB format compatible entry.
Summary for 6I9R
| Entry DOI | 10.2210/pdb6i9r/pdb |
| EMDB information | 4434 |
| Related PRD ID | PRD_000505 |
| Descriptor | 39S ribosomal protein L32, mitochondrial, 39S ribosomal protein L41, mitochondrial, 16S rRNA, ... (57 entities in total) |
| Functional Keywords | ribosome, mitochondria |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 53 |
| Total formula weight | 1745244.15 |
| Authors | Modelska, A.,Aibara, S.,Amunts, A. (deposition date: 2018-11-25, release date: 2020-07-08, Last modification date: 2024-07-10) |
| Primary citation | 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 Cited by 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: 33910005DOI: 10.1016/j.celrep.2021.109024 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.9 Å) |
Structure validation
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