Details

Autor(en) / Beteiligte

• Li, Yong
• Choi, Mihwa
• Cavey, Greg
• Daugherty, Jennifer
• Suino, Kelly
• Kovach, Amanda
• Bingham, Nathan C.
• Kliewer, Steven A.
• Xu, H.Eric

Titel

Crystallographic Identification and Functional Characterization of Phospholipids as Ligands for the Orphan Nuclear Receptor Steroidogenic Factor-1

Ist Teil von

• Molecular cell, 2005-02, Vol.17 (4), p.491-502

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2005

Link zum Volltext

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• The orphan nuclear receptor steroidogenic factor 1 (SF-1) regulates the differentiation and function of endocrine glands. Although SF-1 is constitutively active in cell-based assays, it is not known whether this transcriptional activity is modulated by ligands. Here, we describe the 1.5 Å crystal structure of the SF-1 ligand binding domain in complex with an LXXLL motif from a coregulator protein. The structure reveals the presence of a phospholipid ligand in a surprisingly large pocket (∼1600 Å 3), with the receptor adopting the canonical active conformation. The bound phospholipid is readily exchanged and modulates SF-1 interactions with coactivators. Mutations designed to reduce the size of the SF-1 pocket or to disrupt hydrogen bonds with the phospholipid abolish SF-1/coactivator interactions and significantly reduce SF-1 transcriptional activity. These findings provide evidence that SF-1 is regulated by endogenous ligands and suggest an unexpected relationship between phospholipids and endocrine development and function.