8ekc

Escherichia coli 70S ribosome bound to thermorubin, deacylated P-site tRNAfMet and aminoacylated A-site Phe-tRNA

spinqualitylabelsall models 8ekc, resolution 2.70Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8ekc is a 10 chain structure with sequence from Escherichia coli. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 2.7Å Ligands: 1MG, 2MA, 2MG, 3TD, 4D4, 4OC, 4SU, 5MC, 5MU, 6MZ, D2T, G7M, H2U, IAS, MA6, MEQ, MG, MIA, MS6, OMC, OMG, OMU, PHE, PSU, T8B, UR3, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function RS4_ECOLI One of two assembly initiator proteins for the 30S subunit, it binds directly to 16S rRNA where it nucleates assembly of the body of the 30S subunit. With S5 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). Plays a role in mRNA unwinding by the ribosome, possibly by forming part of a processivity clamp. Protein S4 is also a translational repressor protein, it controls the translation of the alpha-operon (which codes for S13, S11, S4, RNA polymerase alpha subunit, and L17) by binding to its mRNA. Also functions as a rho-dependent antiterminator of rRNA transcription, increasing the synthesis of rRNA under conditions of excess protein, allowing a more rapid return to homeostasis. Binds directly to RNA polymerase. Publication Abstract from PubMed Thermorubin (THR) is an aromatic anthracenopyranone antibiotic active against both Gram-positive and Gram-negative bacteria. It is known to bind to the 70S ribosome at the intersubunit bridge B2a and was thought to inhibit factor-dependent initiation of translation and obstruct the accommodation of tRNAs into the A site. Here, we show that thermorubin causes ribosomes to stall in vivo and in vitro at internal and termination codons, thereby allowing the ribosome to initiate protein synthesis and translate at least a few codons before stalling. Our biochemical data show that THR affects multiple steps of translation elongation with a significant impact on the binding stability of the tRNA in the A site, explaining premature cessation of translation. Our high-resolution crystal and cryo-EM structures of the 70S-THR complex show that THR can co-exist with P- and A-site tRNAs, explaining how ribosomes can elongate in the presence of the drug. Remarkable is the ability of THR to arrest ribosomes at the stop codons. Our data suggest that by causing structural re-arrangements in the decoding center, THR interferes with the accommodation of tRNAs or release factors into the ribosomal A site. Insights into the molecular mechanism of translation inhibition by the ribosome-targeting antibiotic thermorubin.,Paranjpe MN, Marina VI, Grachev AA, Maviza TP, Tolicheva OA, Paleskava A, Osterman IA, Sergiev PV, Konevega AL, Polikanov YS, Gagnon MG Nucleic Acids Res. 2023 Jan 11;51(1):449-462. doi: 10.1093/nar/gkac1189. PMID:36546783 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Ribosome 3D structures

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