inter-domain linker. This is a first demonstration that a hybrid de novo/natural receptor can undergo signaling, and it provides a foundation for future engineering to test biophysical principles and build orthogonal signaling systems! www.biorxiv.org/content/10.1...

which then perturbs the equilibrium of coupled domains downstream. We show that it is possible for a de novo sensor to transmit binding information and initiate a signal transduction cascade, but that signaling is sensitive to the stability of the sensor domain and the length and phase of the 3/4

of thermodynamic signaling in multi-domain signaling receptors had advanced sufficiently to let us make a new-to-nature sensor domain from first principles. This requires that the sensor bind a ligand of interest and that binding triggers a change in the thermodynamic equilibrium of the sensor 2/4