Conformational changes in the ribosome induced by translational miscoding agents.
Ribosomes are dynamic complexes responsible for translating the genetic information encoded in mRNAs to proteins. The accuracy of this process is vital to the survival of an organism, and is often compromised by translational miscoding agents. Aminoglycosides are a group of miscoding agents that bind to the ribosome and reduce the fidelity of translation. Previous studies have shown that aminoglycosides alter the higher order structure of the ribosome. Here, we used a toeprinting assay to how that streptomycin, neomycin, kanamycin, gentamycin, and hygromycin B trigger conformational changes within Escherichia coli ribosome. Miscoding agents viomycin and 30% ethanol also cause similar structural changes within the ribosome. In contrast, antibiotics that do not cause miscoding, such as tetracycline, chloramphenicol, erythromycin, fusidic acid and spectinomycin, do not induce the conformational changes triggered by miscoding agents. Furthermore, ribosomes isolated from strains that are either streptomycin resistant or dependent for growth do not show these conformational changes in the presence of streptomycin. These results correlate structural changes in the ribosome induced by miscoding agents in vitro with their in vivo phenotype.
Jerinic
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O
Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0314, USA.
Joseph
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D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001483:Base Sequence; D004352:Drug Resistance, Microbial; D004926:Escherichia coli / Q000737:chemistry / Q000187:drug effects / Q000235:genetics; D005798:Genes, Bacterial / Q000235:genetics; D009154:Mutation; D014176:Protein Biosynthesis / Q000187:drug effects*; D011487:Protein Conformation / Q000187:drug effects; D023302:Protein Footprinting; D012329:RNA, Bacterial / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012343:RNA, Transfer / Q000235:genetics / Q000378:metabolism; D012270:Ribosomes / Q000737:chemistry* / Q000187:drug effects* / Q000378:metabolism; D014756:Viomycin / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D012329:RNA, Bacterial; D012333:RNA, Messenger; D012343:RNA, Transfer; D014756:Viomycin