5jte
From Proteopedia
Cryo-EM structure of an ErmBL-stalled ribosome in complex with A-, P-, and E-tRNA
Structural highlights
FunctionRS5_ECOLI With S4 and S12 plays an important role in translational accuracy. Many suppressors of streptomycin-dependent mutants of protein S12 are found in this protein, some but not all of which decrease translational accuracy (ram, ribosomal ambiguity mutations).[1] Located at the back of the 30S subunit body where it stabilizes the conformation of the head with respect to the body.[2] The physical location of this protein suggests it may also play a role in mRNA unwinding by the ribosome, possibly by forming part of a processivity clamp.[3] Publication Abstract from PubMedNascent polypeptides can induce ribosome stalling, regulating downstream genes. Stalling of ErmBL peptide translation in the presence of the macrolide antibiotic erythromycin leads to resistance in Streptococcus sanguis. To reveal this stalling mechanism we obtained 3.6-A-resolution cryo-EM structures of ErmBL-stalled ribosomes with erythromycin. The nascent peptide adopts an unusual conformation with the C-terminal Asp10 side chain in a previously unseen rotated position. Together with molecular dynamics simulations, the structures indicate that peptide-bond formation is inhibited by displacement of the peptidyl-tRNA A76 ribose from its canonical position, and by non-productive interactions of the A-tRNA Lys11 side chain with the A-site crevice. These two effects combine to perturb peptide-bond formation by increasing the distance between the attacking Lys11 amine and the Asp10 carbonyl carbon. The interplay between drug, peptide and ribosome uncovered here also provides insight into the fundamental mechanism of peptide-bond formation. A combined cryo-EM and molecular dynamics approach reveals the mechanism of ErmBL-mediated translation arrest.,Arenz S, Bock LV, Graf M, Innis CA, Beckmann R, Grubmuller H, Vaiana AC, Wilson DN Nat Commun. 2016 Jul 6;7:12026. doi: 10.1038/ncomms12026. PMID:27380950[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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Categories: Escherichia coli | Large Structures | Arenz S | Beckmann R | Bock LV | Graf M | Grubmueller H | Innis CA | Vaiana AC | Wilson DN
