| Abstract: |
This chapter explains the three-dimensional structure and complex function of steroid/nuclear receptors. The lipophilic hormones such as the steroids and thyroids have provided a time-honored paradigm for the mechanism of long-distance intercellular communication. The diffusable hormone, representing the signal, originates in one tissue but subsequently affects the growth or activity of target cells in a second tissue at some distance. The receptor proteins are evolutionarily related, as evidenced by their high sequence homology. They share a characteristic modular organization whereby separable functions are encoded by discrete functional domains that encompass ligand-binding, DNA-binding, nuclear localization, and transcriptional modulation. In all steroid/nuclear receptors, the DNA-binding domain is followed by a region of extensive sequence variability, which in turn is followed by the comparatively well conserved ligand-binding domain. It is found that the two amphipathic helices of the nuclear receptors pack together to form a well-conserved hydrophobic core that ultimately link the two zinc-binding pockets together. © 1994, Academic Press Inc. |
