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Article
Nature Structural & Molecular Biology - 13, 871 - 878 (2006)
Published online: 24 September 2006; Corrected online: 19 October 2006 | doi:10.1038/nsmb1145


There is an Erratum (November 2006) associated with this Article.

The antibiotic kasugamycin mimics mRNA nucleotides to destabilize tRNA binding and inhibit canonical translation initiation

Frank Schluenzen1, 4, Chie Takemoto2, 4, Daniel N Wilson1, 4, Tatsuya Kaminishi2, 4, Joerg M Harms1, Kyoko Hanawa-Suetsugu2, Witold Szaflarski1, Masahito Kawazoe2, Mikako Shirouzu2, Knud H Nierhaus1, Shigeyuki Yokoyama2, 3 & Paola Fucini1

1  Max-Planck Institute for Molecular Genetics, D-14195 Berlin, Germany.

2  RIKEN Genomic Sciences Center, 1-7-22 Suehiro-cho, Tsurumi, Yokohama 230-0045, Japan.

3  Department of Biophysics and Biochemistry, Graduate School of Science, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.

4  These authors contributed equally to this work.

Correspondence should be addressed to Paola Fucini fucini@molgen.mpg.de or Shigeyuki Yokoyama yokoyama@biochem.s.u-tokyo.ac.jp

Kasugamycin (Ksg) specifically inhibits translation initiation of canonical but not of leaderless messenger RNAs. Ksg inhibition is thought to occur by direct competition with initiator transfer RNA. The 3.35-Å structure of Ksg bound to the 30S ribosomal subunit presented here provides a structural description of two Ksg-binding sites as well as a basis for understanding Ksg resistance. Notably, neither binding position overlaps with P-site tRNA; instead, Ksg mimics codon nucleotides at the P and E sites by binding within the path of the mRNA. Coupled with biochemical experiments, our results suggest that Ksg indirectly inhibits P-site tRNA binding through perturbation of the mRNA-tRNA codon-anticodon interaction during 30S canonical initiation. In contrast, for 70S-type initiation on leaderless mRNA, the overlap between mRNA and Ksg is reduced and the binding of tRNA is further stabilized by the presence of the 50S subunit, minimizing Ksg efficacy.
*NOTE: In the version of this article initially published, the author name Mikako Shirouzo was spelled incorrectly. The correct author name is Mikako Shirouzu. This error has been corrected in the HTML and PDF versions of the article.

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ISSN: 1545-9993
EISSN: 1545-9985
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