PMID:11389850

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Citation

Spahn, CM, Blaha, G, Agrawal, RK, Penczek, P, Grassucci, RA, Trieber, CA, Connell, SR, Taylor, DE, Nierhaus, KH and Frank, J (2001) Localization of the ribosomal protection protein Tet(O) on the ribosome and the mechanism of tetracycline resistance. Mol. Cell 7:1037-45

Abstract

Tet(O) belongs to a class of ribosomal protection proteins that mediate tetracycline resistance. It is a G protein that shows significant sequence similarity to elongation factor EF-G. Here we present a cryo-electron microscopic reconstruction, at 16 A resolution, of its complex with the E. coli 70S ribosome. Tet(O) was bound in the presence of a noncleavable GTP analog to programmed ribosomal complexes carrying fMet-tRNA in the P site. Tet(O) is directly visible as a mass close to the A-site region, similar in shape 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 the Tet(O) case, does not overlap with the ribosomal A site but is directly adjacent to the primary tetracycline binding site. Our findings give insights into the mechanism of tetracycline resistance.

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Keywords

Bacterial Proteins/chemistry; Bacterial Proteins/metabolism; Bacterial Proteins/pharmacology; Binding Sites; Carrier Proteins; Cryoelectron Microscopy; Escherichia coli/chemistry; Models, Molecular; Molecular Conformation; Protein Biosynthesis/drug effects; Protein Structure, Tertiary; RNA-Binding Proteins/chemistry; RNA-Binding Proteins/metabolism; RNA-Binding Proteins/pharmacology; Ribosomes/chemistry; Ribosomes/metabolism; Tetracycline Resistance/physiology

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