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Structural basis for TetM-mediated tetracycline resistance. 2012

Alexandra Dönhöfer, and Sibylle Franckenberg, and Stephan Wickles, and Otto Berninghausen, and Roland Beckmann, and Daniel N Wilson
Gene Center and Department for Biochemistry, University of Munich, 81377 Munich, Germany.

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.

UI MeSH Term Description Entries
D007091 Image Processing, Computer-Assisted A technique of inputting two-dimensional or three-dimensional images into a computer and then enhancing or analyzing the imagery into a form that is more useful to the human observer. Biomedical Image Processing,Computer-Assisted Image Processing,Digital Image Processing,Image Analysis, Computer-Assisted,Image Reconstruction,Medical Image Processing,Analysis, Computer-Assisted Image,Computer-Assisted Image Analysis,Computer Assisted Image Analysis,Computer Assisted Image Processing,Computer-Assisted Image Analyses,Image Analyses, Computer-Assisted,Image Analysis, Computer Assisted,Image Processing, Biomedical,Image Processing, Computer Assisted,Image Processing, Digital,Image Processing, Medical,Image Processings, Medical,Image Reconstructions,Medical Image Processings,Processing, Biomedical Image,Processing, Digital Image,Processing, Medical Image,Processings, Digital Image,Processings, Medical Image,Reconstruction, Image,Reconstructions, Image
D008958 Models, Molecular Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures. Molecular Models,Model, Molecular,Molecular Model
D004352 Drug Resistance, Microbial The ability of microorganisms, especially bacteria, to resist or to become tolerant to chemotherapeutic agents, antimicrobial agents, or antibiotics. This resistance may be acquired through gene mutation or foreign DNA in transmissible plasmids (R FACTORS). Antibiotic Resistance,Antibiotic Resistance, Microbial,Antimicrobial Resistance, Drug,Antimicrobial Drug Resistance,Antimicrobial Drug Resistances,Antimicrobial Resistances, Drug,Drug Antimicrobial Resistance,Drug Antimicrobial Resistances,Drug Resistances, Microbial,Resistance, Antibiotic,Resistance, Drug Antimicrobial,Resistances, Drug Antimicrobial
D004926 Escherichia coli A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc. Alkalescens-Dispar Group,Bacillus coli,Bacterium coli,Bacterium coli commune,Diffusely Adherent Escherichia coli,E coli,EAggEC,Enteroaggregative Escherichia coli,Enterococcus coli,Diffusely Adherent E. coli,Enteroaggregative E. coli,Enteroinvasive E. coli,Enteroinvasive Escherichia coli
D001426 Bacterial Proteins Proteins found in any species of bacterium. Bacterial Gene Products,Bacterial Gene Proteins,Gene Products, Bacterial,Bacterial Gene Product,Bacterial Gene Protein,Bacterial Protein,Gene Product, Bacterial,Gene Protein, Bacterial,Gene Proteins, Bacterial,Protein, Bacterial,Proteins, Bacterial
D012270 Ribosomes Multicomponent ribonucleoprotein structures found in the CYTOPLASM of all cells, and in MITOCHONDRIA, and PLASTIDS. They function in PROTEIN BIOSYNTHESIS via GENETIC TRANSLATION. Ribosome
D013293 Enterococcus faecalis A species of gram-positive, coccoid bacteria commonly isolated from clinical specimens and the human intestinal tract. Most strains are nonhemolytic. Streptococcus Group D,Streptococcus faecalis
D013752 Tetracycline A naphthacene antibiotic that inhibits AMINO ACYL TRNA binding during protein synthesis. 4-Epitetracycline,Achromycin,Achromycin V,Hostacyclin,Sustamycin,Tetrabid,Tetracycline Hydrochloride,Tetracycline Monohydrochloride,Topicycline,4 Epitetracycline
D016296 Mutagenesis Process of generating a genetic MUTATION. It may occur spontaneously or be induced by MUTAGENS. Mutageneses
D017931 DNA Primers Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques. DNA Primer,Oligodeoxyribonucleotide Primer,Oligodeoxyribonucleotide Primers,Oligonucleotide Primer,Oligonucleotide Primers,Primer, DNA,Primer, Oligodeoxyribonucleotide,Primer, Oligonucleotide,Primers, DNA,Primers, Oligodeoxyribonucleotide,Primers, Oligonucleotide

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