Extended Data Fig. 3: Impact of tuned communication on the VMR and CMR design scenarios.

Possible mechanism of activation for VMR (top) and CMR (bottom) based on the level of communication (coupling) between sensor and responder. Left: without ligand. In the low communication mode, the sensor only weakly interacts with the responder. Hence, the responder can readily occupy its preferred active conformation and trigger high levels of basal activity. In the high communication mode, the sensor strongly influences and shifts the responder towards the inactive conformation, turning off the basal activity. Right: with ligand. In the low communication mode, a saturating ligand concentration pushes all remaining inactive receptors into the active state, producing the maximum signal. In the high communication mode, the sensor’s state is intimately tied to the responder, therefore if all sensors switch to the active state on ligand binding, so too do all responders, producing a potent signaling response. Parts of the figure were generated with bioRender.