What is the effect of cooperative binding on the hemoglobin binding curve?

Cooperative binding refers to the phenomenon where the binding of a ligand to one subunit of a multi-subunit protein influences the binding affinity of subsequent ligand molecules to other subunits. Hemoglobin is a classic example of this, featuring four subunits that can each bind to oxygen.

When the first oxygen molecule binds to hemoglobin, it induces a conformational shift in the protein structure that enhances the affinity of the remaining unbound sites for oxygen. This sequential increase in binding affinity results in a sigmoidal (S-shaped) curve when plotting the fraction of oxygen-saturated hemoglobin against the oxygen concentration. The sigmoidal shape is a key characteristic of cooperative binding, reflecting that at low oxygen concentrations, binding is more challenging, but once one oxygen is bound, the likelihood of further binding increases sharply as more sites become available due to the cooperative effects.

In contrast, independent binding would lead to a hyperbolic binding curve, while entirely eliminating the T-state, which represents the lower affinity form of hemoglobin, would disrupt the mechanism of binding cooperativity entirely and would negate the physiological adaptability of hemoglobin. Thus, the creation of a sigmoidal binding curve is a direct result of cooperative binding in hemoglobin, making this option the