H
IPR035500

Nuclear hormone receptor-like domain superfamily

InterPro entry
Short nameNHR-like_dom_sf
Overlapping entries
 

Description

Steroid or nuclear hormone receptors constitute an important superfamily of transcription regulators that are involved in widely diverse physiological functions, including control of embryonic development, cell differentiation and homeostasis. The receptors function as dimeric molecules in nuclei to regulate the transcription of target genes in a ligand-responsive manner. Nuclear hormone receptors consist of a highly conserved DNA-binding domain that recognises specific sequences (
IPR001628
), connected via a linker region to a C-terminal ligand-binding domain. In addition, certain nuclear hormone receptors have an N-terminal modulatory domain (
IPR046944
). The ligand-binding domain acts in response to ligand binding, which caused a conformational change in the receptor to induce a response, thereby acting as a molecular switch to turn on transcriptional activity
[3]
. For example, after binding of the glucocorticoid receptor to the corticosteroid ligand, the receptor is induced to perform functions ranging from nuclear translocation, oligomerization, cofactor/kinase/transcription factor association, and DNA binding
[2]
. The ligand-binding domain is a flexible unit, where the binding of a ligand stabilises its conformation, which in turn favours coactivator binding to modify receptor activity
[1]
; the coactivator can bind to the activator function 2 (AF2) site at the C-terminal end of the ligand-binding domain
[4]
. The binding of different ligands can alter the conformation of the ligand-binding domain, which ultimately affects the DNA-binding specificity of the DNA-binding domain. In the absence of ligand, steroid hormone receptors are thought to be weakly associated with nuclear components.

This entry represents the all helical domain involved in ligand-binding.

References

1.Coactivator proteins as determinants of estrogen receptor structure and function: spectroscopic evidence for a novel coactivator-stabilized receptor conformation. Tamrazi A, Carlson KE, Rodriguez AL, Katzenellenbogen JA. Mol. Endocrinol. 19, 1516-28, (2005). View articlePMID: 15661830

2.Structure and function of the glucocorticoid receptor ligand binding domain. Bledsoe RK, Stewart EL, Pearce KH. Vitam. Horm. 68, 49-91, (2004). View articlePMID: 15193451

3.The role of coactivators and corepressors in the biology and mechanism of action of steroid hormone receptors. Edwards DP. 5, 307-24, (2000). View articlePMID: 14973393

4.Delineation of a unique protein-protein interaction site on the surface of the estrogen receptor. Kong EH, Heldring N, Gustafsson JA, Treuter E, Hubbard RE, Pike AC. Proc. Natl. Acad. Sci. U.S.A. 102, 3593-8, (2005). View articlePMID: 15728727

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