Mechanism of tetracycline resistance byribosomal protection protein Tet(O)

摘要

Tetracycline resistance protein Tet(O), which protects the bacterial ribosome from bindingthe antibiotic tetracycline, is a translational GTPase with significant similarity in bothsequence and structure to the elongation factor EF-G. Here, we present an atomic modelof the Tet(O)-bound 70S ribosome based on our cryo-electron microscopic reconstruction at9.6-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 threeamino-acid tips of these loops by a single glycine residue result in loss of Tet(O)-mediatedtetracycline resistance. On the basis of these findings, the mechanism of Tet(O)-mediatedtetracycline resistance can be explained in molecular detail.