Protein Name

Ligand-binding domain of human nuclear receptor liver receptor homolog 1 (hLRH-1) in complex with the NR box 1 motif of human SHP


Homo sapiens (human)

Biological Context

Various small, hydrophobic signal molecules function by directly entering cells and binding to various receptors. These receptors then bind to DNA at specific sequences and regulate the transcription of the genes in that region. These genes further regulate the transcription of other genes resulting in a complex pattern of change in gene expression. The receptors are structurally related and form a large family called the nuclear receptor (NR) superfamily. All nuclear receptors have a DNA binding domain (DBD) with which they bind to specific sequences of DNA, and a ligand binding domain (LBD) where the signal molecules bind. Some nuclear receptors are primarily found in the cytosol and translocate to the nucleus upon ligand binding. Others are already bound to specific DNA sequences and activated upon ligand binding. Almost all of the nuclear receptors are bound to inhibitory protein complexes when inactive. Ligand binding changes the conformation of the receptor to free it from the inhibitory protein complex and expose the binding site for transcriptional coactivator proteins. Coactivator proteins bind these sites on the nuclear receptor and induce gene transcription. The NR superfamily is divided into various subfamilies based on sequence identity. The human nuclear receptor liver receptor homolog 1 (hLRH-1) is a receptor belonging to the subfamily NR-5. hLRH-1 has so far been an orphan receptor since its ligand was not known. It functions in the regulation of expression of genes involved in cholesterol and lipid absorption, bile acid efflux and reverse cholesterol transport. LRH-1 is known to bind the small heterodimer partner (SHP) which is a nuclear receptor without a DBD. SHP acts as an LRH-1 co-repressor.

Structure Description


The structure of hLRH-1 LBD above shows a phospholipid and the SHP NR box 1 motif bound to hLRH1. The activity of hLRH-1 is controlled in response to the binding of the phospholipids indicating that it functions as the ligand. SHP NR box 1 motif binds to the groove on the surface of hLRH-1 while the phospholipid binds to the ligand-binding pocket. The presence of a phospholipid as the ligand for hLRH-1 indicates that nuclear phospholipids may play a significant role in transcriptional regulation.

Protein Data Bank (PDB)



  • Ortlund, E.A. Lee, Y. Solomon, I.H. Hager, J.M. Safi, R. Choi, Y. Guan, Z. Tripathy, A. Raetz, C.R.H. McDonnell, D.P. Moore, D.D. Redinbo, M.R.; "Modulation of human nuclear receptor LRH-1 activity by phospholipids and SHP"; Nat.Struct.Mol.Biol.; (2005) 12:357-363 PubMed:15723037.


author: Ashwini Patil

Japanese version:PDB:1YUC