Jean-Marie Boeynaems

The two-step model of ligand-receptor interaction.

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 the 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.

A negative control model of hormone receptor interaction

An original model of hormone-receptor interaction is proposed: the hormone would interact with its receptor by dissociating a regulatory unit from a catalytic unit, which, freed from the negative constraint exerted by the regulatory unit, would become active. It is shown that such a model shares some features with negatively cooperative models: 1. Scatchard plot has a hyperbolic shape; 2. Dissociation of bound labeled hormone, promoted by chemical dilution is enhanced by an excess of cold hormone. A new graph, in which the ratio between the square of bound hormone concentration and the free hormone concentration is plotted against the bound hormone concentration, allows a discrimination between both models. Moreover, the behavior of a negatively controlled receptor unlike a negatively cooperative one, is critically dependent on its physical state (soluble or particulate). The possible application of this model to hormone responsive adenylate cyclases and other biochemical systems, such as cAMP dependent protein kinases, is mentioned.