Figure 1.

Schematic representation of homotropic allosteric models for a dimeric protein. ○ and □ correspond to subunits in binding-incompetent, and binding-competent states, respectively. (a) Monod-Wyman-Changeux (MWC): The symmetry of the dimer is preserved, so that only ○○ and □□ states are permitted. In the absence of ligand, both states are populated, while ligand binding forces the dimer into the □□ state. If the initial equilibrium favors the ○ ○ state, binding is positively cooperative, since the energetic cost of the ○ ○ to □ □ transition is paid by binding the first, but not the second ligand. Note that in the standard MWC model, both ○ ○ and □ □ bind ligand, but with different affinities. For the sake of simplicity we have shown the limiting case where ○ ○ is binding-incompetent. (b) Koshland-Nemethy-Filmer (KNF): Each subunit converts from the ○ to the ○ state only upon binding ligand. Cooperativity is explained in terms of the strengths subunit-subunit interactions. If the transition from the ○ ○ to ○ □ interface is energetically more favorable than from the ○ □ to □ □, binding is negatively cooperative, and the first ligand is bound more strongly than the second. If the transition from the ○ ○ to ○ □ interface is less favorable than from the ○ □ to □ □, binding is positively cooperative, and the second ligand is bound more strongly than the first. (c) Hilser-Thompson (HT): In this case, ○ and □ correspond to the unfolded and folded states, respectively. Each unbound subunit can populate either the folded or unfolded state, and the folding equilibrium is influenced by the state of the adjacent monomer. If folding (□) of one subunit promotes folding (□) of the adjacent subunit, binding is positively cooperative. Conversely, if folding (□) of one subunit promotes unfolding (○) of the adjacent subunit, binding is negatively cooperative.