Mechanism of the nuclear receptor molecular switch

Trends Biochem Sci. 2004 Jun;29(6):317-24. doi: 10.1016/j.tibs.2004.04.006.


Nuclear receptors are central to the regulation of development, endocrine signalling and metabolism. The transcriptional activity of many receptors is controlled through the binding of small, fat-soluble molecules to the ligand-binding domain. In most cases, ligand binding turns the receptors into potent activators of transcription. This switch involves the exchange of co-regulator proteins that mediate transcriptional regulation. Structural and biochemical studies have together revealed the mechanism of action of this ligand-induced molecular switch, in which changes in the dynamic behaviour of the receptor play a key role. This remarkable dynamic mechanism has facilitated the evolution of a family of nuclear receptors with highly diverse ligand recognition and signalling properties.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Gene Expression Regulation
  • Humans
  • Ligands
  • Molecular Structure
  • Protein Conformation
  • Receptors, Cytoplasmic and Nuclear / metabolism
  • Receptors, Cytoplasmic and Nuclear / physiology*
  • Signal Transduction
  • Transcription, Genetic


  • Ligands
  • Receptors, Cytoplasmic and Nuclear