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Structure of E. coli 30S-IF1-IF3-mRNA-Kasugamycin complex
Structural highlights
FunctionRS12_ECOLI With S4 and S5 plays an important role in translational accuracy.[HAMAP-Rule:MF_00403_B] Interacts with and stabilizes bases of the 16S rRNA that are involved in tRNA selection in the A site and with the mRNA backbone. Located at the interface of the 30S and 50S subunits, it traverses the body of the 30S subunit contacting proteins on the other side and probably holding the rRNA structure together. The combined cluster of proteins S8, S12 and S17 appears to hold together the shoulder and platform of the 30S subunit (By similarity).[HAMAP-Rule:MF_00403_B] Cryo-EM studies suggest that S12 contacts the EF-Tu bound tRNA in the A-site during codon-recognition. This contact is most likely broken as the aminoacyl-tRNA moves into the peptidyl transferase center in the 50S subunit.[HAMAP-Rule:MF_00403_B] Publication Abstract from PubMedDuring 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 A. 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. The translation inhibitors kasugamycin, edeine and GE81112 target distinct steps during 30S initiation complex formation.,Safdari HA, Morici M, Sanchez-Castro A, Dallape A, Paternoga H, Giuliodori AM, Fabbretti A, Milon P, Wilson DN Nat Commun. 2025 Mar 12;16(1):2470. doi: 10.1038/s41467-025-57731-8. PMID:40075065[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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