It has been estimated that there are 48 nuclear receptor genes in the human genome. These code for a superfamily of proteins that can regulate gene transcription in response to a wide range of natural and synthetic ligands, including classical steroid hormones, vitamins, intermediate metabolites, xenobiotics and drugs. The first three-dimensional structures for isolated receptor domains appeared 25 years ago with the solution and crystal structures of the glucocorticoid and estrogen receptor DNA binding domains. The intervening years have seen an explosion in structures for the DNA and ligand binding domains of nearly all family members, culminating in the recent emergence of almost complete three-dimensional descriptions for nuclear receptor complexes bound to cognate response elements. These dramatic advances in structural analysis are paralleled by the growing evidence linking nuclear receptor function to normal physiological processes and disease. The insights gained from nuclear receptor structures have the potential to be translated into new drugs for major diseases, including cancer, metabolic syndrome and cardiovascular diseases.

In this book we have brought together a range of review articles to highlight current areas of nuclear receptor research, with the focus on structure and function and translational opportunities for drug discovery. In the first part, the attention is on receptor complexes (Chaps. 6 and 7), allosteric regulation and the role of the intrinsically disordered NTD (Chap. 5) and the role of DNA binding and response element architecture (Chap. 4).