Cooperativity
Definition and meaning of Cooperativity in chemistry.
Cooperativity describes how a multi-subunit protein's affinity for a ligand at one binding site changes because a ligand has already bound at another site, usually producing a sigmoidal (S-shaped) rather than hyperbolic binding curve.
In more detail
In positive cooperativity, binding of the first ligand triggers a conformational shift that increases affinity at the remaining sites; in negative cooperativity, the opposite occurs and affinity drops. Cooperativity is quantified using the Hill equation: a Hill coefficient (n_H) greater than 1 indicates positive cooperativity, n_H equal to 1 indicates no cooperativity (simple hyperbolic binding), and n_H less than 1 indicates negative cooperativity. This behavior lets proteins respond sharply to small changes in ligand concentration, which is physiologically important for efficient gas transport and metabolic regulation.
Key facts
| Field | Biochemistry |
|---|---|
| Quantified by | Hill coefficient (n_H) |
| Classic example | Hemoglobin, n_H ≈ 2.8-3 |
| Curve shape | Sigmoidal (positive) vs. hyperbolic (n_H = 1) |
Hemoglobin exhibits positive cooperativity toward oxygen (Hill coefficient ≈ 2.8-3): binding of O2 to one heme group shifts the tetramer from the low-affinity T state toward the high-affinity R state, so each successive O2 binds more easily. This produces the sigmoidal oxygen-hemoglobin dissociation curve that allows efficient O2 loading in the lungs and release in respiring tissues.
Frequently asked questions
What is the difference between positive and negative cooperativity?
Positive cooperativity means binding at one site increases affinity at the remaining sites, giving a sigmoidal binding curve and Hill coefficient greater than 1 (e.g., hemoglobin). Negative cooperativity means binding decreases affinity at the remaining sites, giving a Hill coefficient less than 1.
How is cooperativity measured experimentally?
It is measured with a Hill plot, graphing log[θ/(1-θ)] against log[ligand concentration], where θ is fractional saturation; the slope of the linear region gives the Hill coefficient.