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A structural basis for streptomycin-induced misreading of the genetic code

Author

Listed:
  • Hasan Demirci

    (Cell Biology and Biochemistry, Brown University)

  • Frank Murphy

    (NE-CAT/Cornell University)

  • Eileen Murphy

    (Cell Biology and Biochemistry, Brown University)

  • Steven T. Gregory

    (Cell Biology and Biochemistry, Brown University)

  • Albert E. Dahlberg

    (Cell Biology and Biochemistry, Brown University)

  • Gerwald Jogl

    (Cell Biology and Biochemistry, Brown University)

Abstract

During protein synthesis, the ribosome selects aminoacyl-transfer RNAs with anticodons matching the messenger RNA codon present in the A site of the small ribosomal subunit. The aminoglycoside antibiotic streptomycin disrupts decoding by binding close to the site of codon recognition. Here we use X-ray crystallography to define the impact of streptomycin on the decoding site of the Thermus thermophilus 30S ribosomal subunit in complexes with cognate or near-cognate anticodon stem–loop analogues and messenger RNA. Our crystal structures display a significant local distortion of 16S ribosomal RNA induced by streptomycin, including the crucial bases A1492 and A1493 that participate directly in codon recognition. Consistent with kinetic data, we observe that streptomycin stabilizes the near-cognate anticodon stem–loop analogue complex, while destabilizing the cognate anticodon stem–loop analogue complex. These data reveal how streptomycin disrupts the recognition of cognate anticodon stem–loop analogues and yet improves recognition of a near-cognate anticodon stem–loop analogue.

Suggested Citation

  • Hasan Demirci & Frank Murphy & Eileen Murphy & Steven T. Gregory & Albert E. Dahlberg & Gerwald Jogl, 2013. "A structural basis for streptomycin-induced misreading of the genetic code," Nature Communications, Nature, vol. 4(1), pages 1-8, June.
    • Handle: RePEc:nat:natcom:v:4:y:2013:i:1:d:10.1038_ncomms2346
    DOI: 10.1038/ncomms2346
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    Cited by:

    1. Dylan Girodat & Hans-Joachim Wieden & Scott C. Blanchard & Karissa Y. Sanbonmatsu, 2023. "Geometric alignment of aminoacyl-tRNA relative to catalytic centers of the ribosome underpins accurate mRNA decoding," Nature Communications, Nature, vol. 14(1), pages 1-15, December.

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