Abstract

Aminoglycosides are widely used antibiotics that cause messenger RNA decoding errors, block mRNA and transfer RNA translocation, and inhibit ribosome recycling. Ribosome recycling follows the termination of protein synthesis and is aided by ribosome recycling factor (RRF) in bacteria. The molecular mechanism by which aminoglycosides inhibit ribosome recycling is unknown. Here we show in X-ray crystal structures of the Escherichia coli 70S ribosome that RRF binding causes RNA helix H69 of the large ribosomal subunit, which is crucial for subunit association, to swing away from the subunit interface. Aminoglycosides bind to H69 and completely restore the contacts between ribosomal subunits that are disrupted by RRF. These results provide a structural explanation for aminoglycoside inhibition of ribosome recycling.

1. Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA.
2. Department of Molecular and Cell Biology, University of California, Berkeley, California 94720, USA.
3. Department of Chemistry, University of California, Berkeley, California 94720, USA.
4. Department of Biochemistry and Biophysics, University of California, San Francisco, California 94158, USA.
5. Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
6. Department of Biochemistry and Molecular Biology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
7. Present addresses: Cancer Research UK London Research Institute, Clare Hall Laboratories, South Mimms, Hertfordshire EN6 3LD, UK (B.S.S.) and National Cardiovascular Center Research Institute, Osaka, Japan (G.H.).
8. These authors contributed equally to this work.

Correspondence to: Jamie H Doudna Cate^1,2,3 e-mail: jcate@lbl.gov

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