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

The tetracycline repressor (TetR) regulates the most abundant resistance me chanism against the antibiotic tetracycline in gram-negative bacteria. The TetR protein and its mutants are commonly used as control elements to regul ate 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 ngstrom 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 sta rting with C-terminal unwinding and shifting of the short helix alpha 6 in each monomer. This forces a pendulum-like motion of helix alpha 4, which in creases the separation of the attached DNA binding domains by 3 Angstrom, a bolishing the affinity of TetR for its operator DNA.