Classification and Structure of Nuclear Receptors

Like other transcriptional regulators, nuclear receptors exhibit a modular structure with different regions corresponding to autonomous functional domains. At the level of the primary structure the steroid hormone receptors can be divided into five different domains (Fig. 4.3), each with specific functions. 

The steroid hormone receptors are sequence-specific DNA-binding proteins whose cognate DNA elements are termed hormone-responsive elements (HREs). The HREs known to date possess a common structure. They are composed primarily of two copies of a hexamer sequence. In Table 4.1 are listed the hexamer sequences of the HREs of important nuclear receptors. 

The identity of an H RE is determined by the sequence, polarity, and distance of the hexamers. Mutation and duplication of an ancestral recognition sequence have al- 

The receptors bind to the cognate H RE mainly as dimers, allowing the formation of homodimers as well as heterodimers between various receptor monomers. We know of very few nuclear receptors whose H RE contains only a single copy of the recognition sequence. These receptors bind as monomers to the cognate HRE. 

Based on the subunit structure of DNA-bound receptors and on the structure of the HREs, four classes of nuclear receptors can be distinguished (Fig. 4.5). 

A typical nuclear receptor contains a domain responsible for the DNA binding (domain C), the ligand binding and dimerization (E), and for the transactivation and other protein-protein interactions (A,B,E,F). Furthermore, there are also nuclear localization signals (D). 

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