Abstract
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-Å 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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Bacterial Proteins / chemistry
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Bacterial Proteins / metabolism*
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Bacterial Proteins / ultrastructure
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Campylobacter jejuni / metabolism*
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Carrier Proteins / chemistry
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Carrier Proteins / metabolism*
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Carrier Proteins / ultrastructure
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Cryoelectron Microscopy
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Guanosine Triphosphate / analogs & derivatives
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Guanosine Triphosphate / chemistry
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Guanosine Triphosphate / metabolism
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Models, Molecular
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Molecular Sequence Data
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Mutant Proteins / chemistry
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Mutant Proteins / metabolism
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Protein Binding
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Protein Structure, Secondary
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Protein Structure, Tertiary
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RNA, Transfer / chemistry
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RNA, Transfer / metabolism
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Ribosomal Proteins / chemistry
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Ribosomal Proteins / metabolism*
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Ribosome Subunits, Large, Bacterial / metabolism
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Ribosome Subunits, Large, Bacterial / ultrastructure
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Ribosome Subunits, Small, Bacterial / metabolism
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Ribosome Subunits, Small, Bacterial / ultrastructure
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Ribosomes / metabolism
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Ribosomes / ultrastructure
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Structural Homology, Protein
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Tetracycline Resistance*
Substances
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Bacterial Proteins
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Carrier Proteins
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GDPNP compound
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Mutant Proteins
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Ribosomal Proteins
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Tet O resistance protein, Bacteria
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Guanosine Triphosphate
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RNA, Transfer