THE RELATION BETWEEN COOPERATIVITY IN LIGAND BINDING AND INTRAMOLECULAR COOPERATIVITY IN ALLOSTERIC PROTEINS

摘要

An analysis of the relation between cooperativity in ligand binding by an allosteric protein and cooperativity in intramolecular interactions within the protein is presented. An intramolecular interaction between two residues, a and b, may be detected and measured by construction of a double-mutant cycle comprising wild-type protein, two single mutants and the corresponding double mutant. Higher-order interactions between three or more residues may be measured by using multidimensional mutant space. The analogy between the Koshland-Nemethy-Filmer (KNF) model for cooperativity in ligand binding and double-mutant cycles is demonstrated. It is shown that cooperativity in ligand binding due to KNF-type allosteric transitions must involve cooperativity in intramolecular interactions. Thus, in certain ideal cases, the Hill coefficient for cooperativity in ligand binding may be expressed as a function of the extent of cooperativity between interactions in the protein as measured by multidimensional mutant cycles. [References: 10]