Conformational changes of the Tet repressor induced by tetracycline trapping

Abstract

The X-ray crystal structure analysis of inducer-free Tet repressor, TetR, at 2.4 Å resolution identifies one of two openings of the tunnel-like binding site as the entrance for the inducer tetracycline-Mg 2+, [Mg Tc] +. Recognition and binding of the inducer unleashes conformational changes leading to the induced state of TetR. In the first step, the C-terminal turn of α-helix 6 unwinds, thereby altering the orientation of α-helix 4. This different orientation of α-helix 4 is stabilized by a series of hydrogen bonds mediated through a chain of eight water molecules. The α-helix 4 connects the DNA-binding domain (α-helices 1 to 3) to the rigid TetR core, and thus regulates gene expression through its respective orientations.