6i9r

From Proteopedia

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

PDB ID 6i9r

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Structural highlights

6i9r is a 10 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , , , , , , , , , , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

RM09_HUMAN

Publication Abstract from PubMed

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.

Inhibition of mitochondrial translation suppresses glioblastoma stem cell growth.,Sighel D, Notarangelo M, Aibara S, Re A, Ricci G, Guida M, Soldano A, Adami V, Ambrosini C, Broso F, Rosatti EF, Longhi S, Buccarelli M, D'Alessandris QG, Giannetti S, Pacioni S, Ricci-Vitiani L, Rorbach J, Pallini R, Roulland S, Amunts A, Mancini I, Modelska A, Quattrone A Cell Rep. 2021 Apr 27;35(4):109024. doi: 10.1016/j.celrep.2021.109024. PMID:33910005^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Sighel D, Notarangelo M, Aibara S, Re A, Ricci G, Guida M, Soldano A, Adami V, Ambrosini C, Broso F, Rosatti EF, Longhi S, Buccarelli M, D'Alessandris QG, 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. 2021 Apr 27;35(4):109024. doi: 10.1016/j.celrep.2021.109024. PMID:33910005 doi:http://dx.doi.org/10.1016/j.celrep.2021.109024