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          Institute: MPI für molekulare Genetik     Collection: Ribosome Research Groups     Display Documents

ID: 174937.0, MPI für molekulare Genetik / Ribosome Research Groups
Mechanism of Tet(O)-mediated tetracycline resistance
Authors:Connell, Sean R.; Trieber, Catharine A.; Dinos, George P.; Einfeldt, Edda; Taylor, Diane E.; Nierhaus, Knud H.
Date of Publication (YYYY-MM-DD):2003-02-17
Title of Journal:EMBO Journal
Journal Abbrev.:Embo J.
Issue / Number:4
Start Page:945
End Page:953
Copyright:© European Molecular Biology Organization
Review Status:not specified
Audience:Experts Only
Abstract / Description:Tet(O) is an elongation factor-like protein which confers resistance to the protein synthesis inhibitor tetracycline by promoting the release of the drug from its inhibitory site on the ribosome. Here we investigated the interaction of Tet(O) with the elongating ribosome and show, using dimethyl sulfate (DMS) probing and binding assays, that it interacts preferentially with the post-translocational ribosome. Furthermore, using an XTP-dependent mutant of Tet(O), we demonstrated that Tet(O) induces conformational rearrangements within the ribosome which can be detected by EF-Tu, and manifested as a stimulation in the GTPase activity of this elongation factor. As such, these conformational changes probably involve the ribosomal GTPase-associated center and, accordingly, Tet(O) alters the DMS modification pattern of the L11 region. Additionally, tetracycline binding is associated with an Ea of 58 kJ/mol. These results suggest a model where both Tet(O) and tetracycline induce a conformational change in functionally opposite directions and the Tet(O)-induced conformation persists after it has left the ribosome; this prevents rebinding of the drug while allowing productive A-site occupation by a ternary complex in the presence of tetracycline.
Free Keywords:antibiotic resistance; protein synthesis; ribosome; Tet(O); tetracycline
Comment of the Author/Creator:Date: 2003, Feb 17
External Publication Status:published
Document Type:Article
Communicated by:Ribosome Group
Affiliations:MPI für molekulare Genetik
External Affiliations:Max Planck Inst Mol Genet, D-14195 Berlin, Germany.; Univ Alberta, Dept Med Microbiol & Immunol, Edmonton, AB T6G 2H7, Canada.; Univ Alberta, Dept Biol Sci, Edmonton, AB T6G 2H7, Canada.; Univ Patras, Sch Med, Biochem Lab, GR-26110 Patras, Greece
Identifiers:ISI:000181280100019 [ID No:1]
ISSN:0261-4189 [ID No:2]
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