CONFORMATIONAL-CHANGES OF THE TET REPRESSOR INDUCED BY TETRACYCLINE TRAPPING

The X-ray crystal structure analysis of inducer-free Tet repressor, Te tR, at 2.4 Angstrom resolution identifies one of two openings of the t unnel-like binding site as the entrance for the inducer tetracycline-M g2+, [Mg Tc](+). Recognition and binding of the inducer unleashes conf ormational changes leading to the induced state of TetR. In the first step, the C-terminal turn of alpha-helix 6 unwinds, thereby altering t he orientation of alpha-helix 4. This different orientation of alpha-h elix 4 is stabilized by a series' of hydrogen bonds mediated through a chain of eight water molecules. The alpha-helix 4 connects the DNA-bi nding domain (alpha-helices 1 to 3) to the rigid TetR core, and thus r egulates gene expression through its respective orientations. (C) 1998 Academic Press Limited.