Mechanism of tetracycline resistance by ribosomal protection protein Tet(O)

作者:Li Wen; Atkinson Gemma C; Thakor Nehal S; Allas Uelar; Lu Chuao chao; Chan Kwok Yan; Tenson Tanel; Schulten Klaus; Wilson Kevin S; Hauryliuk Vasili; Frank Joachim*
来源:Nature Communications, 2013, 4(1): 1477.
DOI:10.1038/ncomms2470

摘要

Tetracycline resistance protein Tet(O), which protects the bacterial ribosome from binding the antibiotic tetracycline, is a translational GTPase with significant similarity in both sequence and structure to the 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-angstrom 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 result 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.