1YUC

Human Nuclear Receptor Liver Receptor Homologue-1, LRH-1, Bound to Phospholipid and a Fragment of Human SHP

Summary for 1YUC

• Entry DOI: 10.2210/pdb1yuc/pdb
• Descriptor: Orphan nuclear receptor NR5A2, Nuclear receptor 0B2, L-ALPHA-PHOSPHATIDYL-BETA-OLEOYL-GAMMA-PALMITOYL-PHOSPHATIDYLETHANOLAMINE, ... (5 entities in total)
• Functional Keywords: liver receptor homologue 1; nuclear receptor ligand binding domain; lrh-1; phospholipid; shp; small heterodimer partner, transcription regulation
• Biological source: Homo sapiens (human); More
• Cellular location: Nucleus : O00482 Q15466
• Total number of polymer chains: 4
• Total formula weight: 63515.28

Authors

Ortlund, E.A.,Yoonkwang, L.,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. (deposition date: 2005-02-13, release date: 2005-03-01, Last modification date: 2024-02-14)

Primary citation

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., 12:357-363, 2005

PubMed Abstract: The human nuclear receptor liver receptor homolog 1 (hLRH-1) plays an important role in the development of breast carcinomas. This orphan receptor is efficiently downregulated by the unusual co-repressor SHP and has been thought to be ligand-independent. We present the crystal structure at a resolution of 1.9 A of the ligand-binding domain of hLRH-1 in complex with the NR box 1 motif of human SHP, which we find contacts the AF-2 region of hLRH-1 using selective structural motifs. Electron density indicates phospholipid bound within the ligand-binding pocket, which we confirm using mass spectrometry of solvent-extracted samples. We further show that pocket mutations reduce phospholipid binding and receptor activity in vivo. Our results indicate that hLRH-1's control of gene expression is mediated by phospholipid binding, and establish hLRH-1 as a novel target for compounds designed to slow breast cancer development.

PubMed: 15723037
DOI: 10.1038/nsmb910

Experimental method

X-RAY DIFFRACTION (1.9 Å)