4DOR
Human Nuclear Receptor Liver Receptor Homologue-1, LRH-1, in its apo State Bound to a Fragment of Human SHP Box1
Summary for 4DOR
| Entry DOI | 10.2210/pdb4dor/pdb |
| Related | 4DOR |
| Descriptor | Nuclear receptor subfamily 5 group A member 2, Nuclear receptor subfamily 0 group B member 2, L-ALPHA-PHOSPHATIDYL-BETA-OLEOYL-GAMMA-PALMITOYL-PHOSPHATIDYLETHANOLAMINE, ... (4 entities in total) |
| Functional Keywords | nuclear receptor, ligand binding domain, phospholipids, nr5a, diabetes, phosphatidylcholine, transcription |
| Biological source | Homo sapiens (human) More |
| Cellular location | Nucleus : O00482 Q15466 |
| Total number of polymer chains | 4 |
| Total formula weight | 62529.06 |
| Authors | Musille, P.M.,Ortlund, E.A. (deposition date: 2012-02-10, release date: 2012-04-18, Last modification date: 2024-02-28) |
| Primary citation | Musille, P.M.,Pathak, M.C.,Lauer, J.L.,Hudson, W.H.,Griffin, P.R.,Ortlund, E.A. Antidiabetic phospholipid-nuclear receptor complex reveals the mechanism for phospholipid-driven gene regulation. Nat.Struct.Mol.Biol., 19:532-537, 2012 Cited by PubMed Abstract: The human nuclear receptor liver receptor homolog-1 (LRH-1) has an important role in controlling lipid and cholesterol homeostasis and is a potential target for the treatment of diabetes and hepatic diseases. LRH-1 is known to bind phospholipids, but the role of phospholipids in controlling LRH-1 activation remains highly debated. Here we describe the structure of both apo LRH-1 and LRH-1 in complex with the antidiabetic phospholipid dilauroylphosphatidylcholine (DLPC). Together with hydrogen-deuterium exchange MS and functional data, our studies show that DLPC binding is a dynamic process that alters co-regulator selectivity. We show that the lipid-free receptor undergoes previously unrecognized structural fluctuations, allowing it to interact with widely expressed co-repressors. These observations enhance our understanding of LRH-1 regulation and highlight its importance as a new therapeutic target for controlling diabetes. PubMed: 22504882DOI: 10.1038/nsmb.2279 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.9 Å) |
Structure validation
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