Overview of the structural basis for transcription regulation by nuclear hormone receptors.
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.
Kumar
Raj
R
Department of Human Biological Chemistry & Genetics, University of Texas Medical Branch, 5.104 Medical Research Bldg., Galveston, TX 77555, U.S.A.
Johnson
Betty H
BH
Thompson
E Brad
EB
D000818:Animals; D001665:Binding Sites; D005786:Gene Expression Regulation; D006801:Humans; D017434:Protein Structure, Tertiary; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry / Q000502:physiology*; D040681:Structural Homology, Protein; D014158:Transcription, Genetic
D018160:Receptors, Cytoplasmic and Nuclear