The family of nuclear receptors contains about 50 soluble receptors found within the interior of cells. They sense lipophilic ligands. Ligand binding to nuclear receptors results in a change in conformation, which allows formation complexes with other proteins and DNA binding in order to regulate gene expression.
The general structure of a nuclear receptors consists of 5 distinguishable domains:
The N-terminal regulatory domain contains an activation function which is independent of the presence of ligand.
The DNA-binding domain is highly conserved domain which binds to specific sequences of DNA (hormone response elements).
The hinge region connects the DNA-binding
domain with the ligand-binding domain.
The ligand-binding domain is moderately conserved in sequence. The ligand binding cavity is within the interior of this domain. It also contains a second activation function, which binds co-activator and co-repressor proteins, dependent on the presence of bound ligand.
The C-terminal domain is variable in sequence between various nuclear receptors and is important for protein sorting. Nuclear receptors may be classified according to their mechanism of action (homo- or hetero-dimerisation, binding to (inverted) hormone responsive element) and distribution within the cell when no ligand is present (cytosol or nucleus).