cooperativity: one construct, many systems

In biochemistry, cooperativity is the phenomenon in which binding of one ligand to a multi-site molecule changes the affinity of the remaining sites, so the binding curve becomes sigmoidal rather than hyperbolic. Adair's 1925 The hemoglobin system: VI. The oxygen dissociation curve of hemoglobin quantified this for haemoglobin, where each bound oxygen makes the next bind more readily. The referent is an interaction among binding sites that sharpens a molecule's response to ligand concentration, the same construct later seen in polymer helix-coil transitions and formalised in allosteric pharmacology.[1]

Unit

The degree to which one site's binding alters others' affinity (e.g., the Hill coefficient)

Recovery means

Not applicable

Measured by

Read from the steepness of the binding curve, summarised by the Hill coefficient or the Adair constants

In physical chemistry, cooperativity describes transitions in chain molecules that switch almost all-or-none because each converted unit makes its neighbours more likely to convert. Zimm and Bragg's 1959 Theory of the phase transition between helix and random coil in polypeptide chains modelled the helix-coil transition with a cooperativity parameter that sets how sharp the switch is. The referent is neighbour-coupled switching along a chain, the same cooperative construct as ligand binding in haemoglobin, here governing a conformational change rather than site occupancy.[2]

Unit

The sharpness of a chain's all-or-none transition (cooperativity parameter)

Recovery means

Not applicable

Measured by

Captured by the transition width and the Zimm-Bragg cooperativity parameter from spectroscopic melting curves

In molecular pharmacology, cooperativity is formalised by the allosteric model: an oligomeric protein shifts between tense and relaxed conformations, and ligand binding tips the equilibrium so that later binding events are favoured, producing a cooperative dose-response. Monod, Wyman, and Changeux's 1965 On the nature of allosteric transitions: A plausible model gave the concerted account that explains sigmoidal binding and allosteric drug action. The referent is conformation-linked coupling between binding sites that governs how steeply a receptor or enzyme responds to a ligand, the same cooperativity construct as in haemoglobin and in helix-coil chains.[3]

Unit

The conformational coupling that makes a receptor's response to ligand sigmoidal

Recovery means

Not applicable

Measured by

Inferred from sigmoidal dose-response or binding data fitted to the MWC (concerted) allosteric model