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• W2000417208 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." @default.
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• W2000417208 date "2012-04-15" @default.
• W2000417208 modified "2023-10-14" @default.
• W2000417208 title "Antidiabetic phospholipid–nuclear receptor complex reveals the mechanism for phospholipid-driven gene regulation" @default.
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• W2000417208 doi "https://doi.org/10.1038/nsmb.2279" @default.
• W2000417208 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3960984" @default.
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