Figure 1.

(a) Allosteric (“Hill-type”) cooperativity provides a means of overcoming the 81-fold dynamic range of single site receptors (red) to produce steeper, more responsive behavior (blue). Cooperativity arises when multiple binding sites interact such that the first binding event improves the affinity of subsequent binding events. (b) To design this we employ the population-shift mechanism, in which the first binding event is coupled to an unfavorable conformational change, reducing its affinity (K_D1) relative to that of the second binding event (K_D2). (c) While maximal cooperativity (dashed lines) is only achieved if the second binding event is infinitely more favorable than the first, near-ideal behavior is rapidly approached as the relative affinity of the subsequent binding event rises. (d) Even modest cooperativity significantly improves sensitivity to small changes in concentration (shown here as the relative change in occupancy per two-fold change in target concentration).