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Structural basis of gene regulation by the tetracycline inducible Tet repressor-operator system.

TitleStructural basis of gene regulation by the tetracycline inducible Tet repressor-operator system.
Publication TypeJournal Article
Year of Publication2000
AuthorsOrth P, Schnappinger D, Hillen W, Saenger W, Hinrichs W
JournalNat Struct Biol
Volume7
Issue3
Pagination215-9
Date Published2000 Mar
ISSN1072-8368
KeywordsAllosteric Regulation, Amino Acid Substitution, Bacterial Proteins, Base Sequence, Binding Sites, Crystallography, X-Ray, Dimerization, DNA-Binding Proteins, Escherichia coli, Gene Expression Regulation, Bacterial, Magnesium, Models, Molecular, Molecular Sequence Data, Nucleic Acid Conformation, Oligodeoxyribonucleotides, Operator Regions, Genetic, Protein Conformation, Repressor Proteins, Sequence Homology, Signal Transduction, Structure-Activity Relationship, Substrate Specificity, Tetracycline
Abstract

The tetracycline repressor (TetR) regulates the most abundant resistance mechanism against the antibiotic tetracycline in grain-negative bacteria. The TetR protein and its mutants are commonly used as control elements to regulate gene expression in higher eukaryotes. We present the crystal structure of the TetR homodimer in complex with its palindromic DNA operator at 2.5 A resolution. Comparison to the structure of TetR in complex with the inducer tetracycline-Mg2+ allows the mechanism of induction to be deduced. Inducer binding in the repressor core initiates conformational changes starting with C-terminal unwinding and shifting of the short helix a6 in each monomer. This forces a pendulum-like motion of helix a4, which increases the separation of the attached DNA binding domains by 3 A, abolishing the affinity of TetR for its operator DNA.

DOI10.1038/73324
Alternate JournalNat Struct Biol
PubMed ID10700280

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