cooperativity
Summary
Cooperativity is when ligand binding at one site on a multisubunit protein changes the affinity of its other sites for that ligand. In positive cooperativity, as with hemoglobin and O₂, this gives a sigmoidal binding curve instead of the hyperbola of a single-site protein.
Detail
Meaning: Binding at one site changes the affinity of the other sites on the same protein. In positive cooperativity each bound ligand makes the next binding easier. In hemoglobin, O₂ binding favors a shift from the low-affinity tense (T) state toward the high-affinity relaxed (R) state. Two accepted models describe this: the concerted (MWC) model, where subunits switch states together, and the sequential (KNF) model, where they change one at a time.
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 (mol/L raised to the power n). n > 1 means positive, n = 1 none, n < 1 negative cooperativity.
On the MCAT: Hemoglobin's O₂ curve is sigmoidal, while myoglobin, with one site, gives a hyperbola. The steep middle means a small change in pO₂ causes a large change in saturation, so hemoglobin loads O₂ in the lungs and unloads it in the tissues.
Common confusion: A right shift of the curve (higher P50, caused by H⁺, CO₂ or 2,3-BPG) changes affinity but does not remove cooperativity; the curve stays sigmoidal. Also, n is not the number of sites: hemoglobin has four, but its n is below 4.
Sources
- Lehninger Principles of Biochemistry
- Biochemistry (Berg, Tymoczko, Stryer)
- Campbell Biology
Written for the MCAT and checked before it was published. For study reference only. Spotted an error? Let us know.