4DOR

Human Nuclear Receptor Liver Receptor Homologue-1, LRH-1, in its apo State Bound to a Fragment of Human SHP Box1

4DOR の概要

• エントリーDOI: 10.2210/pdb4dor/pdb
• 関連するPDBエントリー: 4DOR
• 分子名称: 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)
• 機能のキーワード: nuclear receptor, ligand binding domain, phospholipids, nr5a, diabetes, phosphatidylcholine, transcription
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Nucleus : O00482 Q15466
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 62529.06

構造登録者

Musille, P.M.,Ortlund, E.A. (登録日: 2012-02-10, 公開日: 2012-04-18, 最終更新日: 2024-02-28)

主引用文献

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

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: 22504882
DOI: 10.1038/nsmb.2279

実験手法

X-RAY DIFFRACTION (1.9 Å)