Overview of the structural basis for transcription regulation by nuclear hormone receptors

Essays Biochem. 2004;40:27-39. doi: 10.1042/bse0400027.

Abstract

The mechanism of action of the nuclear hormone receptors (NHRs) as gene- regulatory molecules has become a major focus of current biological interest. NHRs belong to the superfamily of ligand-activated transcription factors, which are involved in the regulation of homoeostasis, reproduction, development and differentiation. To fully understand their functions, it is important to know the functional three-dimensional structure of these proteins. Molecular cloning and structure-function analyses have revealed that NHRs commonly have three functional regions: the N-terminal, DNA-binding and ligand-binding domains. Structures of some of these domains expressed independently have been solved. However, to date the three-dimensional structure remains unknown for full-length and even for any two domains together of any NHR family member. The available structures nevertheless begin to give clues of how site-specific DNA binding takes place, and how ligand binding alters the ligand-binding domain, consequently affecting potential interactions of the NHRs with co-activators/co-repressors and other components of basal transcriptional machinery. However, precisely how signals from a ligand through its NHR are passed to specific genes is still unknown. Herein, we present a broad overview of current knowledge on the structure and functions of the NHRs.

Publication types

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

MeSH terms

  • Animals
  • Binding Sites
  • Gene Expression Regulation*
  • Humans
  • Protein Structure, Tertiary
  • Receptors, Cytoplasmic and Nuclear / chemistry
  • Receptors, Cytoplasmic and Nuclear / physiology*
  • Structural Homology, Protein
  • Transcription, Genetic*

Substances

  • Receptors, Cytoplasmic and Nuclear