A Novel Equation for Cooperativity of the Allosteric State Function

Stuart J Edelstein

doi:10.1016/j.jmb.2013.09.010

Abstract

The MWC (Monod–Wyman–Changeux) allosteric model postulates concerted conformational changes between two states: the intrinsically more stable T state with relatively weak ligand binding and the R state with relatively strong ligand binding. The model distinguishes between Y¯ (the fractional occupation of the binding sites) and R¯ (the fraction of molecules in the R state). Cooperativity (measured by the Hill coefficient) has strikingly different properties for Y¯ and R¯. For the latter, cooperativity depends only on the relative affinities of the two states, not on their relative intrinsic stabilities, as demonstrated here with a simple new equation relating the Hill coefficient to R¯.

Highlights

The concept of allosteric interactions, introduced a half-century ago [1,2,3], has had a powerful impact in biology for problems of signal transduction and control at various levels [4,5,6,7]
The generalization of allostery is reflected by the fact that, some 50 years after creation of this neologism, “allosteric” as a keyword generates over 18,000 responses in PubMed
The original mathematical formulation in the MWC (Monod–Wyman–Changeux) model for allosteric proteins is based on two distinct conformational states (T and R) related by a single intrinsic equilibrium constant, L, where L = [T]/[R] in the absence of ligands for that protein [3]

Summary

Introduction

The concept of allosteric interactions, introduced a half-century ago [1,2,3], has had a powerful impact in biology for problems of signal transduction and control at various levels [4,5,6,7]. Cooperativity depends only on the relative affinities of the two states, not on their relative intrinsic stabilities, as demonstrated here with a simple new equation relating the Hill coefficient toR. Cooperativity of the Allosteric State Function equation for the Hill coefficient of R , which is presented here.

Results

Conclusion