What history tells us XXVII.

Abstract

The number of articles published on allostery has rapidly increased in recent years. Since the 1960s, the word ‘allostery’ has always had different meanings. On the one hand, allostery simply describes the conformational changes of proteins (and other macromolecules) following the binding of ligands. On the other hand, allostery may explicitly refer to the theory proposed by Jacques Monod, Jeffries Wyman and Jean-Pierre Changeux in 1965 – also known as the MWCmodel, or model of the concerted transition (Monod et al. 1965). In this model, the allosteric change in conformation of proteins is not directly induced by the interaction of the proteins with their effectors, but results from the displacement of equilibrium between conformational states. It is the latter vision of allostery that is flourishing at present, but with three significant extensions: the number of structural states is no longer limited to two but to an ensemble; allostery is not characteristic just of oligomeric proteins comprising different subunits but also concerns monomeric proteins and other macromolecules such as RNAandDNA; and the catalytic process also requires the dynamic reequilibration of an ensemble of pre-existing states. In the new unifying vision, ‘allosteric regulation and catalysis emerge via a common route’ (Goodey and Benkovic 2008). I will successively remind the conditions in which the adjective ‘allosteric’ emerged 50 years ago, and why Monod hypothesized in his model the existence of different states pre-existing in equilibrium. Then I will discuss the different reasons for the recent renewed interest in allostery. And, finally, I will underline the importance, both theoretical and practical, of this new vision, but sharply contrast it with apparently related views on the importance of plasticity in the behaviour of biological systems (West-Eberhard 2003), and on the extension of Darwinism to the molecular level (Kupiec 2009).