TCB Publications - Abstract

Wen Li, Gemma C. Atkinson, Nehal S. Thakor, Ülar Allas, Chuao-chao Lu, Kwok-Yan Chan, Tanel Tenson, Klaus Schulten, Kevin S. Wilson, Vasili Hauryliuk, and Joachim Frank. Mechanism of tetracycline resistance by ribosomal protection protein Tet(O). 4:1477, 2013. (8 pages). (PMC: 3576927)

LI2013 Tetracycline resistance protein Tet(O), which protects the bacterial ribosome from binding with the antibiotic tetracycline, is a translational GTPase with significant similarity in both sequence and structure to elongation factor EF-G. Here, we present an atomic model of the Tet(O)-bound 70S ribosome based on our cryo-electron microscopic reconstruction at 9.6 Å resolution. This atomic model allowed us to identify the Tet(O)- ribosome binding sites, which involve three characteristic loops in domain 4 of Tet(O). Replacements of the three-amino acid tips of these loops by a single glycine residue resulted in loss of Tet(O)- mediated tetracycline resistance. On the basis of these findings, the mechanism of Tet(O)- mediated tetracycline resistance can be explained in molecular detail.

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