Abstract

Control over the sensitivity with which biomolecular receptors respond to small changes in the concentration of their target ligand is crucial to many cellular processes and likely could be of value in many biotechnologies. In nature, this control is often achieved using “Hill-type” allosteric cooperativity, an elegant mechanism that has, unfortunately, hitherto proven difficult to achieve via generalizable design strategies. In response, we demonstrate here a quantitative and apparently versatile means of rationally introducing this useful mechanism into a range of normally noncooperative receptors. We achieve in the best of our examples cooperativity, and thus sensitivity, experimentally indistinguishable from the theoretically expected maximum.