Sequencing of cDNAs derived from mRNAs encoding various nuclear receptors has revealed remarkable conservation in their amino acid sequences. It has also revealed that each of these receptors has three functional regions (Figure 9-43). The first is a unique N-terminal region of variable length (100–500 amino acids). Portions of this variable region function as activation domains in most nuclear receptors. The second is a DNA-binding domain that maps near the center of the primary sequence and contains a repeat of the C4 zinc-finger motif (see Figure 9-30b). The third region, the hormone-binding domain, located near the C-terminal end, contains a hormone-dependent activation domain (see Figure 9-31b, c). In some nuclear receptors, the hormone-binding domain functions as a repression domain in the absence of ligand.
FIGURE 9-43 General design of transcription factors in the nuclear-receptor superfamily. The centrally located DNA-binding domain exhibits considerable sequence homology among different receptors and contains two copies of the C4 zinc-finger motif (see Figure 9-30b). The C-terminal hormone-binding domain exhibits somewhat less homology. The N-terminal regions of various receptors vary in length, have unique sequences, and may contain one or more activation domains. See R. M. Evans, 1988, Science 240:889.