7azy

Context-specific inhibition of eukaryotic translation by macrolide antibiotics

spinqualitylabelsall models 7azy, resolution 2.88Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7azy is a 10 chain structure with sequence from Saccharomyces cerevisiae S288C. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 2.877Å Ligands: TEL Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function RL8A_YEAST Publication Abstract from PubMed Macrolide antibiotics bind in the nascent peptide exit tunnel of the bacterial ribosome and prevent polymerization of specific amino acid sequences, selectively inhibiting translation of a subset of proteins. Because preventing translation of individual proteins could be beneficial for the treatment of human diseases, we asked whether macrolides, if bound to the eukaryotic ribosome, would retain their context- and protein-specific action. By introducing a single mutation in rRNA, we rendered yeast Saccharomyces cerevisiae cells sensitive to macrolides. Cryo-EM structural analysis showed that the macrolide telithromycin binds in the tunnel of the engineered eukaryotic ribosome. Genome-wide analysis of cellular translation and biochemical studies demonstrated that the drug inhibits eukaryotic translation by preferentially stalling ribosomes at distinct sequence motifs. Context-specific action markedly depends on the macrolide structure. Eliminating macrolide-arrest motifs from a protein renders its translation macrolide-tolerant. Our data illuminate the prospects of adapting macrolides for protein-selective translation inhibition in eukaryotic cells. Context-specific action of macrolide antibiotics on the eukaryotic ribosome.,Svetlov MS, Koller TO, Meydan S, Shankar V, Klepacki D, Polacek N, Guydosh NR, Vazquez-Laslop N, Wilson DN, Mankin AS Nat Commun. 2021 May 14;12(1):2803. doi: 10.1038/s41467-021-23068-1. PMID:33990576 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Ribosome 3D structures

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