Type IV

Type III nuclear receptors (principally NR subfamily 2) are similar to type I receptors in that both classes bind to DNA as homodimers. However, type III nuclear receptors, in contrast to type I, bind to direct repeat instead of inverted repeat HREs.

Type III

Type II nuclear receptors include principally subfamily 1, for example the retinoic acid receptor, retinoid X receptor and thyroid hormone receptor.

Type II

Type I nuclear receptors include members of subfamily 3, such as the androgen receptor, estrogen receptors, glucocorticoid receptor, and progesterone receptor.

Ligand binding to type I nuclear receptors in the cytosol results in the dissociation of heat shock proteins, homo-dimerization, translocation from the cytoplasm into the cell nucleus, and binding to specific sequences of DNA known as hormone response elements (HREs). Type I nuclear receptors bind to HREs consisting of two half-sites separated by a variable length of DNA, and the second half-site has a sequence inverted from the first (inverted repeat).

Type I

Small lipophilic substances such as natural hormones diffuse past the cell membrane and bind to nuclear receptors located in the cytosol (type I NR) or nucleus (type II NR) of the cell. This causes a change in the conformation of the receptor, which, depending on the mechanistic class (type I or II), triggers a number of down stream events that eventually results in up or down regulation of gene expression. In addition, two additional classes, type III which are a variant of type I, and type IV that bind DNA as monomers have also been defined.

Nuclear receptors (NRs) may be classified into two broad classes according to their mechanism of action and subcellular distribution in the absence of ligand.

Highly variable in sequence between various nuclear receptors.

Crystallographic structure of the ligand binding domain of RAR-related orphan receptor gamma (LIGAND - 25-hydroxycholesterol).

• F) C-terminal domain:

Type II receptors, in contrast to type I, are retained in the nucleus regardless of the ligand binding status and in addition bind as hetero-dimers to DNA. In the absence of ligand, type II nuclear receptors are often complexed with corepressor proteins. Ligand binding to the nuclear receptor causes dissociation of corepressor and recruitment of coactivator proteins. Additional proteins including RNA polymerase are then recruited to the NR/DNA complexes that transcribe DNA into messenger RNA.

Дата добавления: 2014-01-14