Ricerc@Sapienza

Hemoglobin (Hb) is the prototypical example of a cooperative protein. Cooperativity of Hb is largely accounted for by an allosteric structural change between the T and R quaternary structures. Allostery is such a powerful explanation of Hb cooperativity that the possibility of cooperative events occurring within each allosteric conformation, in the absence of any quaternary structural change has usually been overlooked, and actually experiments specifically aimed at detecting non-allosteric cooperativity have usually failed to do so.

Cooperative ligand binding is a fundamental property of many biological macromolecules, notably transport proteins, hormone receptors, and enzymes. Positive homotropic cooperativity, the form of cooperativity that has greatest physiological relevance, causes the ligand affinity to increase as ligation proceeds, thus increasing the steepness of the ligand binding isotherm. The measurement of the extent of cooperativity has proven difficult, and the most commonly employed marker of cooperativity, the Hill coefficient, originates from a structural hypothesis that has long been disproved.