Cooperativity in Associating Proteins. Monomer-Dimer Equilibrium Coupled to Ligand Binding

Alexander Levitzki, Joseph Schlessinger

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Abstract

The cooperativity due to ligand binding to a protein monomer and a protein dimer in equilibrium was studied. The system is: E + E ⇌ E2(K1); E + S ⇌ ES (K2): ES + E ⇌ E2S (K3); and ES + ES ⇌ E2S2(K4). Using a computer and a plotter, Hill plots for differenct combinations of the parameters K1, K2, K3, and K4 were constructed. It was found that high ratios of K4/K2 with moderate K1 and K2 ensure high positive cooperativity. In such cases the species E2, ES, and E2S never accumulate to significant concentrations throughout the titration. High K4/K2 ratios or high K4 alone does not ensure binding of ligand. The monomer must have a finite affinity toward the ligand in order for the whole binding process to occur. Ratios of K4/K2 lower than 103 generate negative cooperativity and the transient accumulation of E2S in the proteinligand mixture. The possible physiological significance of positive cooperativity due to protein aggregation is discussed.

Original languageEnglish
Pages (from-to)5214-5219
Number of pages6
JournalBiochemistry
Volume13
Issue number25
DOIs
StatePublished - 1 Dec 1974
Externally publishedYes

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