Model of KdpD activation. KdpD exists in two states, an "OFF" and an "ON" state. Upon stimulus perception, the positively charged surface of the Usp domain within the N-terminal region (yellow) faces the positively charged region (R503-R511) [10, 11, 14] in the C-terminal region of KdpD. Thus, electrostatic repulsions between N- and C-terminal domains force the protein into the "open" position. This in turn releases the N-terminal domain, forming a stable complex with KdpE~P and the DNA  initiating kdpFABC expression. Replacement of the KdpD-Usp domain with UspF or UspG results in inversion of the surface net charges. The negative net surface charge of these two proteins forces electrostatic attraction between the N- and the C-terminal regions, leaving KdpD in the "OFF" state under all conditions.