Structural basis for TetM-mediated tetracycline resistance
- 16 October 2012
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 109 (42), 16900-16905
- https://doi.org/10.1073/pnas.1208037109
Abstract
Ribosome protection proteins (RPPs) confer tetracycline resistance by binding to the ribosome and chasing the drug from its binding site. The current model for the mechanism of action of RPPs proposes that drug release is indirect and achieved via conformational changes within the drug-binding site induced upon binding of the RPP to the ribosome. Here we report a cryo-EM structure of the RPP TetM in complex with the 70S ribosome at 7.2-Å resolution. The structure reveals the contacts of TetM with the ribosome, including interaction between the conserved and functionally critical C-terminal extension of TetM and the decoding center of the small subunit. Moreover, we observe direct interaction between domain IV of TetM and the tetracycline binding site and identify residues critical for conferring tetracycline resistance. A model is presented whereby TetM directly dislodges tetracycline to confer resistance.Keywords
This publication has 38 references indexed in Scilit:
- Target- and Resistance-Based Mechanistic Studies with TP-434, a Novel Fluorocycline AntibioticAntimicrobial Agents and Chemotherapy, 2012
- Differential Effects of Thiopeptide and Orthosomycin Antibiotics on Translational GTPasesCell Chemical Biology, 2011
- PSRP1 Is Not a Ribosomal Protein, but a Ribosome-binding Factor That Is Recycled by the Ribosome-recycling Factor (RRF) and Elongation Factor G (EF-G)Published by Elsevier BV ,2010
- Structural Insight into Nascent Polypeptide Chain–Mediated Translational StallingScience, 2009
- The Structure of the Ribosome with Elongation Factor G Trapped in the Posttranslocational StateScience, 2009
- Structural basis for mRNA and tRNA positioning on the ribosomeProceedings of the National Academy of Sciences of the United States of America, 2006
- Functional, Biophysical, and Structural Bases for Antibacterial Activity of TigecyclineAntimicrobial Agents and Chemotherapy, 2006
- Coot: model-building tools for molecular graphicsActa Crystallographica Section D-Biological Crystallography, 2004
- UCSF Chimera?A visualization system for exploratory research and analysisJournal of Computational Chemistry, 2004
- SPIDER and WEB: Processing and Visualization of Images in 3D Electron Microscopy and Related FieldsJournal of Structural Biology, 1996