FIG. 1.

Conformation-based description of allostery (a) canonical descriptors of allostery is based on cooperativity seen in multimeric proteins (like hemoglobin) when they bind their ligands. If the active sites of the monomers are independent, ligand binding curves have a hyperbolic shape like those of Michaelis Menten plots (curve 1). In positive cooperativity, the plot flattens at first and then quickly increases to attain maximal signal (curve 2). The MWC formula is an expression for this S-shaped binding function. Negative cooperativity is seen as a steep rise in binding with early flattening of the curve before optimal binding saturation (curve 3). (b) MWC and KNF models of allostery are based on descriptors of two distinct protein conformations that occupy distinct basins in the free energy landscape. Conformation that has low affinity for the ligand is called the tense state (T-state) and the conformation with high affinity for the ligand is the relaxed state (R-state). (c) The MWC model postulates that the two protein conformations coexist in an equilibrium while the KNF model postulates that ligand binding induces conformational switching and converts one conformation to another. (d) The population shift theory postulates that a protein’s free energy landscape includes an ensemble of varying populations of all probable conformations. Allosteric signals (like ligand binding) choose compatible populations to shift the ensemble to a new averaged conformation.