Localization of the ribosomal protection protein Tet(O) on the ribosome and the mechanism of tetracycline resistance

Tet(O) belongs to a class of ribosomal protection proteins that mediate tet racycline resistance. It is a G protein that shows significant sequence sim ilarity to elongation factor EF-G. Here we present a cryo-electron microsco pic reconstruction, at 16 Angstrom resolution, of its complex with the E. c oli 70S ribosome. Tet(O) was bound in the presence of a noncleavable GTP an alog to programmed ribosomal complexes carrying fMet-tRNA in the P site. Te t(O) is directly visible as a mass close to the A-site region, similar in s hape and binding position to EF-G. However, there are important differences . One of them is the different location of the tip of domain IV, which in t he Tet(O) case, does not overlap with the ribosomal A site but is directly adjacent to the primary tetracycline binding site. Our findings give insigh ts into the mechanism of tetracycline resistance.