The two-step model of ligand-receptor interaction

Abstract

The theoretical properties of a ‘two-step’ receptor, consisting of two independent molecular entities, a regulatory (R) and an effector (E) unit, which are supposed to diffuse freely in the plane of a fluid and mosaic membrane, are presented. The ligand (L)-hormone, drug, neurotransmitter-binds to the regulatory unit (first step), so that it then becomes able to interact with the effector unit (second step) which is then activated. R + L = RL RL + E = RLE → effect This type of receptor can exhibit remarkable properties. (1) The relationship between binding, and to a lesser extent effect, and ligand concentration is negatively cooperative; (2) The degree of negative cooperativity varies biphasically as function of the total concentrations of regulatory and effector units; (3) The relationship between binding and effect is non-linear: the ‘two-step’ model constitutes a plausible explanation for the existence of a ‘receptor reserve’; (4) Kinetics of activation and inactivation can be more or less rapid than kinetics of association and dissociation of the ligand. This model can account for and integrate in a coherent framework many data on membrane receptors. It could also be used to describe the two-step interaction of steroids with their nuclear receptors.