Cooperative Binding - Mechanisms of Cooperativity

Mechanisms of Cooperativity

Two models were hypothesized to account for the binding cooperativity observed in proteins, the MWC model and the KNF model.

The Monod-Wyman-Changeux (MWC) model was advanced by Jacques Monod, Jeffries Wyman and Jean-Pierre Changeux in 1965. It posits that the protein has only two states, a low-affinity state T and a high-affinity state R, where the T state is thermodynamically favored. Hence, at low amounts of bound ligand, the protein prefers the low-affinity T state; however, as the amount of bound ligand increases, the protein comes to prefer the high-affinity state. Structural studies have supported the MWC model and elucidated the R and T states; however, the model cannot explain negative cooperativity.

An alternative model is the sequential or "induced fit" model of Daniel Koshland, George Némethy and Filmer (KNF model), in which ligand binding at one site causes a local conformational change ("induced fit") that causes small conformational changes at nearby binding sites, affecting their affinity for the ligand. Thus, according to the KNF model, the protein has many slightly different conformational states, corresponding to all possible modes of ligand binding.