Receptor/ligand binding diffusion

Each steroid hormone diffuses across the plasma membrane of its target cell and binds to a specific cytosolic or nuclear receptor. These receptor-ligand complexes accumulate in the nucleus, dimerize, and bind to specific regulatory DIMA sequences (hormone-response elements) in association with coactivator proteins, thereby causing promoter activation and increased transcription of targeted genes. 

Because of their hydrophobic character the steroid hormones or other nonpolar ligands diffuse through membranes into cells. There they may encounter a variety of binding proteins that affect their access to a receptor.307 311 Some receptors, including glucocorticoid receptors, are found in the cytosol. After a hor-... 

Some ligands do not interact principally with cell surface receptors, but diffuse into cells and bind to intracellular receptors in the cytoplasm. For example, ligand binding to cytoplasmic steroid receptors initiates a process that is not well understood but that involves the movement of steroid-bound receptor into the cell nucleus, where the receptor molecule interacts with genomic material, resulting in alterations in gene expression and protein synthesis. 

From studies of lipid-water mixtures and isolated membranes the general functional features of the bilayer are known barrier properties, lateral diffusion, acyl chain disorder and protein association. To vmderstand the mechanisms behind a wide spectrum of membrane functions, a detailed picture at the level of local curvature is needed. Examples are fusion processes, cooperativity in receptor/ligand binding or transport through the bilayer of the proteins that are constantly synthesised for export from the endoplasmic reticulum. Some preliminary discussions of the possibilities of curved, rather than flat, membremes follow. 

We will consider the interplay of diffusion and intrinsic binding interactions in three types of situations (1) binding of ligand to receptor when... 

We will begin by looking at the binding of ligand to receptor when both are free in solution (Fig. 9a) and will follow the approach by Shoup and Szabo (1982). Our aim is to obtain expressions for the overall forward and reverse rate constants, k and kr, as they depend on diffusion coefficients and free receptor number. In order to accomplish this, we will calculate the rate at which a ligand molecule would be expected to bind to a receptor molecule by the two-step diffusion and intrinsic reaction process. 

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