Receptor-ligand binding interactions

Isothermal titration calorimetry (ITC) is almost the ultimate titration methodology in that this technique is based entirely upon titration of heat energy and then deconvolution of this information into equilibrium binding constant information. However, the real beauty of this technique is that it engages directly with the thermodynamics of receptor-ligand binding interactions. 

Figure 7.24 Van t Hoff Relationship Plots, (a) Classical linear plots obtained in the event that AW bind is temperature independent over the temperature range studied, (b) Curved plots that characterise the situation when AH md is temperature dependent. Negative curvature is characteristic of the involvement of hydrophobic effect in receptor-ligand binding interactions.

Gronemeyer, H. (2000) Nuclear receptor ligand-binding domains three-dimensional structures, molecular interactions and pharmacological implications. Trends in Pharmacological Sciences, 21, 381-388. 

Figure 14-1. Signaling via G protein-coupled receptors. Ligand binding to its cell-surface receptor initiates interaction of the receptor with the heterotrimeric G protein for which it is specific. A conformational change in the G protein brought about by binding of the ligand-receptor complex promotes exchange of GDP for GTP. The activated Gd-GTP dissociates from the Gp complex and both can interact with effectors, which carry on the signal to the mechanism that implements the cellular response.

Dubbink, H.J., Hersmus, R., Pike, A.C.W., Molier, M., Brinkmann, A.O., Jenster, G. and Trapman, J. (2006) Androgen receptor ligand-binding domain interaction and nuclear receptor specificity of FXXLF and LXXLL motifs as determined by L/F swapping. Molecular Endocrinology, 20, 1742-1755. 

Schmitt, J.D., Sharpies, C.G.V., Caldwell, W.S., 1998. Aromatic-cation interactions in nicotinic acetylcholine receptor ligand binding. In Book of Abstracts, 216th ACS National Meeting, Boston. American Chemical Society, Washington, DC, MEDI-153. 

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