| Literature DB >> 22504882 |
Paul M Musille1, Manish Pathak1, Janelle L Lauer2, William H Hudson1, Patrick R Griffin2, Eric A Ortlund1.
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.Entities:
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Year: 2012 PMID： 22504882 PMCID： PMC3960984 DOI： 10.1038/nsmb.2279
Source DB: PubMed Journal: Nat Struct Mol Biol ISSN： 1545-9985 Impact factor: 15.369