The multiple origins of cooperativity in binding to multi-site lattices

Binding events involving the reversible association of ligands with polymeric lattices of binding sites are common in biology and frequently exhibit significant cooperativity in binding. Positive and negative cooperativity in binding may be detected by characteristic changes in binding curves for multiple binding, compared to the binding expected for simple, independent binding events that are based on combinatorial considerations only. Cooperativity arises from ligand-dependent interactions distinct from binding per se. Ligand-dependent nearest neighbor interactions may be of two types referred to as ligand-lattice (which can only occur if a bound ligand is unneighbored) and ligand-ligand (which can occur if two or more bound ligands are adjacent). The molecular mechanisms underlying these two sources of cooperativity are not the same. Identical cooperative binding curves may be produced by changes from unity in parameters representing either one or both of these interaction types. Positive cooperativity may equally result from destabilizing ligand-lattice interactions that disfavor initial, unneighbored binding, stabilizing ligand-ligand interactions that favor subsequent, neighbored binding, or both. The structural origins of these are different, and cooperativity may emerge from multiple structural interactions.