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.
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Acknowledgements
We thank K. Frankel, S. Classen and G. Meigs for help with data measurement at the SIBYLS and 8.3.1 beamlines at the Advanced Light Source; K. Rajashankar, I. Kourinov and N. Sukumar for help with data measurement at Northeastern Collaborative Access Team beamline 24-IDC at the Advanced Photon Source; W. Wintermeyer, M. O'Connor and K. Fredrick for helpful discussions; A. Borovinskiy for help with figure preparation and overall support; and J. Doudna, H. Noller, P. Gunda and J. Dunkle for helpful comments on the manuscript. This work was supported by US National Institutes of Health (NIH) grants GM65050 (J.H.D.C.) and GM60429 (A.K.), the Nippon Paint Fund (H.K.), NIH National Cancer Institute grant CA92584 (for the SIBYLS and 8.3.1 beamlines), NIH National Center for Research Resources grant RR-15301 (for beamline 24-IDC) and US Department of Energy grants DE-AC03-76SF00098, KP110201, and LBNL LDRD 366851 (J.H.D.C.), DE-AC03 76SF00098 (for the SIBYLS and 8.3.1 beamlines) and DE-AC02-06CH11357 (for the Advanced Photon Source).
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Borovinskaya, M., Pai, R., Zhang, W. et al. Structural basis for aminoglycoside inhibition of bacterial ribosome recycling. Nat Struct Mol Biol 14, 727–732 (2007). https://doi.org/10.1038/nsmb1271
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DOI: https://doi.org/10.1038/nsmb1271
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