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Title | The translation inhibitors kasugamycin, edeine and GE81112 target distinct steps during 30S initiation complex formation. |
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Journal, issue, pages | Nat Commun, Vol. 16, Issue 1, Page 2470, Year 2025 |
Publish date | Mar 12, 2025 |
![]() | Haaris A Safdari / Martino Morici / Ana Sanchez-Castro / Andrea Dallapè / Helge Paternoga / Anna Maria Giuliodori / Attilio Fabbretti / Pohl Milón / Daniel N Wilson / ![]() ![]() ![]() |
PubMed Abstract | During bacterial translation initiation, the 30S ribosomal subunit, initiation factors, and initiator tRNA define the reading frame of the mRNA. This process is inhibited by kasugamycin, edeine and ...During bacterial translation initiation, the 30S ribosomal subunit, initiation factors, and initiator tRNA define the reading frame of the mRNA. This process is inhibited by kasugamycin, edeine and GE81112, however, their mechanisms of action have not been fully elucidated. Here we present cryo-electron microscopy structures of 30S initiation intermediate complexes formed in the presence of kasugamycin, edeine and GE81112 at resolutions of 2.0-2.9 Å. The structures reveal that all three antibiotics bind within the E-site of the 30S and preclude 30S initiation complex formation. While kasugamycin and edeine affect early steps of 30S pre-initiation complex formation, GE81112 stalls pre-initiation complex formation at a further step by allowing start codon recognition, but impeding IF3 departure. Collectively, our work highlights how chemically distinct compounds binding at a conserved site on the 30S can interfere with translation initiation in a unique manner. |
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Methods | EM (single particle) |
Resolution | 2.0 - 2.9 Å |
Structure data | EMDB-50320, PDB-9fco: EMDB-50327, PDB-9fda: EMDB-50476, PDB-9fib: EMDB-50912, PDB-9g06: ![]() EMDB-51214: Structure of Kasugamycin-30S-IF1-IF3-mRNA-tRNA translation pre-initiation complex, open form ![]() EMDB-51217: Structure of Edeine-30S-IF1-IF3-mRNA-tRNA translation pre-initiation complex, open form |
Chemicals | ![]() ChemComp-KSG: ![]() ChemComp-MG: ![]() ChemComp-K: ![]() ChemComp-HOH: ![]() ChemComp-EDE: ![]() PDB-1ic4: |
Source |
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![]() | TRANSLATION / Ribosome / Antibiotic / Ribosomes / 30S subunit / 30S inhibitors / Antibiotics / 30S initiation / Translational inhibitor |