Structural basis for hygromycin B inhibition of protein biosynthesis

  1. Maria A. Borovinskaya1,6,
  2. Shinichiro Shoji2,
  3. Kurt Fredrick2,3, and
  4. Jamie H.D. Cate1,4,5
  1. 1Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA
  2. 2Department of Microbiology, The Ohio State University, Columbus, Ohio 43210, USA
  3. 3Ohio State Biochemistry Program, The Ohio State University, Columbus, OH 43210, USA
  4. 4Department of Chemistry, University of California at Berkeley, Berkeley, California 94720, USA
  5. 5Department of Molecular and Cell Biology, University of California at Berkeley, Berkeley, California 94720, USA

Abstract

Aminoglycosides are one of the most widely used and clinically important classes of antibiotics that target the ribosome. Hygromycin B is an atypical aminoglycoside antibiotic with unique structural and functional properties. Here we describe the structure of the intact Escherichia coli 70S ribosome in complex with hygromycin B. The antibiotic binds to the mRNA decoding center in the small (30S) ribosomal subunit of the 70S ribosome and induces a localized conformational change, in contrast to its effects observed in the structure of the isolated 30S ribosomal subunit in complex with the drug. The conformational change in the ribosome caused by hygromycin B binding differs from that induced by other aminoglycosides. Also, in contrast to other aminoglycosides, hygromycin B potently inhibits spontaneous reverse translocation of tRNAs and mRNA on the ribosome in vitro. These structural and biochemical results help to explain the unique mode of translation inhibition by hygromycin B.

Keywords

Footnotes

  • ↵6 Present address: Department of Cellular and Molecular Pharmacology, University of California at San Francisco, San Francisco, CA 94158, USA.

  • Reprint requests: Jamie H.D. Cate, Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA; e-mail: jcate{at}lbl.gov; fax: (510) 666-2747.

  • Article published online ahead of print. Article and publication date are at http://www.rnajournal.org/cgi/doi/10.1261/rna.1076908.

    • Received March 14, 2008.
    • Accepted May 7, 2008.
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  1. Published in Advance June 20, 2008, doi: 10.1261/rna.1076908 RNA 14: 1590-1599 Copyright © 2008 RNA Society

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