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Functional insights from the structure of the 30S ribosomal subunit and its interactions with antibiotics

Nature volume 407, pages 340348 (21 September 2000) | Download Citation

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Abstract

The 30S ribosomal subunit has two primary functions in protein synthesis. It discriminates against aminoacyl transfer RNAs that do not match the codon of messenger RNA, thereby ensuring accuracy in translation of the genetic message in a process called decoding. Also, it works with the 50S subunit to move the tRNAs and associated mRNA by precisely one codon, in a process called translocation. Here we describe the functional implications of the high-resolution 30S crystal structure presented in the accompanying paper, and infer details of the interactions between the 30S subunit and its tRNA and mRNA ligands. We also describe the crystal structure of the 30S subunit complexed with the antibiotics paromomycin, streptomycin and spectinomycin, which interfere with decoding and translocation. This work reveals the structural basis for the action of these antibiotics, and leads to a model for the role of the universally conserved 16S RNA residues A1492 and A1493 in the decoding process.

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Acknowledgements

This work was supported by the Medical Research Council (UK) and a grant from the US National Institutes of Health to V.R. and S.W.White. D.E.B. was supported by an EMBO long-term fellowship, and W.M.C. by an NIH predoctoral fellowship. We thank R. Ravelli for help with data collection, and M. Pacold for help and discussions with the modelling of antibiotic structures.

Author information

Author notes

    • Andrew P. Carter
    • , William M. Clemons
    •  & Ditlev E. Brodersen

    These authors contributed equally to this work.

Affiliations

  1. †MRC Laboratory of Molecular Biology , Hills Road, Cambridge, UK

    • Andrew P. Carter
    • , William M. Clemons
    • , Ditlev E. Brodersen
    • , Robert J. Morgan-Warren
    • , Brian T. Wimberly
    •  & V. Ramakrishnan
  2. ‡Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, Utah 84132, USA

    • William M. Clemons

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Correspondence to V. Ramakrishnan.

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https://doi.org/10.1038/35030019

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