Orth P, Schnappinger D, Hillen W, Saenger W, Hinrichs W
Institut für Chemie, Kristallographie, Freie Universität Berlin, Takustr. 6, D-14195 Berlin, Germany.
Nat Struct Biol. 2000 Mar;7(3):215-9. doi: 10.1038/73324.
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.
四环素阻遏蛋白（TetR）调控革兰氏阴性菌中对抗生素四环素最普遍的耐药机制。TetR蛋白及其突变体通常用作控制元件来调控高等真核生物中的基因表达。我们展示了TetR同二聚体与其回文DNA操纵子复合物的晶体结构，分辨率为2.5埃。与TetR与诱导剂四环素-Mg2+复合物的结构进行比较，可推导出诱导机制。诱导剂在阻遏蛋白核心中的结合引发构象变化，起始于每个单体中C末端短螺旋a6的解旋和移位。这迫使螺旋a4进行钟摆样运动，使相连的DNA结合结构域之间的距离增加3埃，从而消除TetR对其操纵子DNA的亲和力。
