Figure 3.

A realistic model of signal transduction, inspired by the VirA protein of the VirA/VirG two-component system. (a) In addition to the domains and states in the model presented in Figure 2, there is a cytoplasmic linker domain, with its own active and inactive states, which is modulated by the signaling ligand C. A different ligand, L, modulates the receptor. The total number of states in this system is 64, and for clarity only the fully inactive and the fully active states are diagrammed. (b) Activation, relative to the resting state, is plotted against an increasing concentration of ligand L in the presence of different concentrations of C. This illustrates the ability to integrate signals from multiple ligands. Though this model does not explicitly treat the receptor as being dimeric (as is the case for the VirA protein), it can be easily extended to do so. In this case, the binding of a ligand may or may not be coupled with receptor dimerization, and there may exist cooperativity (negative or positive) between the two ligand-binding sites. Potential scenarios that can be explored include the following: Binding of a single ligand may push the system toward the active state, whereas binding two ligands symmetrically may favor the inactive state; alternatively, the receptor may signal only when two ligands are bound; or binding of the second ligand may proceed independently of the first one.