cooperative binding

Meaning: In a protein with several subunits and binding sites, such as hemoglobin (four subunits, each with a heme), binding at one site shifts the protein's conformation. In positive cooperativity, this shift favors the high-affinity R (relaxed) state, so each additional O₂ binds more easily. The T (tense) state has low affinity. Binding of O₂ stabilizes R, and the remaining subunits follow. Negative cooperativity, where binding lowers affinity at other sites, also exists but is tested less often.

Equation: Hill equation, log[Y/(1 − Y)] = n log[L] − log K′, where Y is fractional saturation (unitless), [L] is free ligand concentration (mol/L), n is the Hill coefficient (unitless), and K′ is a constant. n > 1 means positive cooperativity, n = 1 means none, and n < 1 means negative cooperativity.

On the MCAT: Passages show O₂ saturation curves. Hemoglobin gives a sigmoidal curve, while myoglobin (a single subunit, no cooperativity) gives a hyperbola with higher affinity (lower P₅₀). You may be asked how a right shift (from lower pH, higher CO₂, higher 2,3-BPG, or higher temperature) changes loading in the lungs and unloading in the tissues. The same idea applies to allosteric enzymes, which show sigmoidal v versus [S] curves.

Common confusion: Cooperativity is not the same as high affinity. Myoglobin binds O₂ more tightly than hemoglobin but is not cooperative. The steep middle of the sigmoid curve is what lets hemoglobin load O₂ in the lungs and release it in tissues over a small change in pO₂.