cooperativity

Cooperativity is a common phenomenon in biochemistry and biophysics where the binding of a ligand to one site of a multimeric protein affects the binding properties of other sites. This interdependence among binding sites can increase (positive cooperativity) or decrease (negative cooperativity) the overall affinity, and it often produces sigmoidal, rather than hyperbolic, binding curves.

The mechanism typically involves allosteric interactions: changes in conformation or subunit arrangement propagate through the molecule, so the state of one site influences neighboring sites. Cooperativity is central to many regulatory proteins, receptors, and enzymes, enabling switch-like responses to small changes in ligand concentration.

Two foundational theoretical frameworks describe cooperative behavior. The Monod-Wyman-Changeux (MWC) concerted model posits that subunits simultaneously transition between low-affinity and high-affinity states. The Koshland-Némethy-Filmer (KNF) sequential model assumes subunits change state one at a time in a stepwise fashion. Both models can account for sigmoidal binding curves and allosteric regulation observed in real systems.

Quantification often uses the Hill coefficient (nH). Values greater than 1 indicate positive cooperativity, equal to 1 suggests noncooperative binding, and less than 1 implies negative cooperativity. Hemoglobin is a classic example of positive cooperativity for oxygen binding, with oxygen affinity increasing as more sites become occupied. Hemoglobin also exhibits heterotropic regulation by factors such as pH, CO2, and 2,3-bisphosphoglycerate, which modulate binding without occupying the same sites.

Cooperativity extends beyond oxygen transport to enzymes with multiple binding sites, receptors, and multimeric channels, reflecting a general strategy for precise, coordinated biological responses.