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

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-? 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.