4DOS
Human Nuclear Receptor Liver Receptor Homologue-1, LRH-1, Bound to DLPC and a Fragment of TIF-2
Summary for 4DOS
| Entry DOI | 10.2210/pdb4dos/pdb |
| Related | 4DOR |
| Descriptor | Nuclear receptor subfamily 5 group A member 2, Nuclear receptor coactivator 2, PENTAETHYLENE GLYCOL, ... (5 entities in total) |
| Functional Keywords | nuclear receptor, ligand binding domain, phospholipids, nr5a, diabetes, phosphatidylcholine, dlpc, transcription |
| Biological source | Homo sapiens (human) More |
| Cellular location | Nucleus (Probable): O00482 Nucleus: Q15596 |
| Total number of polymer chains | 3 |
| Total formula weight | 32669.74 |
| 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 (2 Å) |
Structure validation
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