1YP0

Structure of the steroidogenic factor-1 ligand binding domain bound to phospholipid and a SHP peptide motif

Summary for 1YP0

• Entry DOI: 10.2210/pdb1yp0/pdb
• Descriptor: nuclear receptor subfamily 5, group A, member 1, Nuclear receptor subfamily 0, group B, member 2, DI-PALMITOYL-3-SN-PHOSPHATIDYLETHANOLAMINE, ... (4 entities in total)
• Functional Keywords: ligand dependent nuclear receptor, steroidogenic factor-1, nr5a1, helical sandwich fold, lbd fold, transcription
• Biological source: Mus musculus (house mouse); More
• Cellular location: Nucleus: P33242; Cytoplasm : P97947
• Total number of polymer chains: 2
• Total formula weight: 29517.50

Authors

Li, Y.,Choi, M.,Cavey, G.,Daugherty, J.,Suino, K.,Kovach, A.,Bingham, N.,Kliewer, S.,Xu, H. (deposition date: 2005-01-28, release date: 2005-04-19, Last modification date: 2024-02-14)

Primary citation

Li, Y.,Choi, M.,Cavey, G.,Daugherty, J.,Suino, K.,Kovach, A.,Bingham, N.,Kliewer, S.,Xu, H.
Crystallographic identification and functional characterization of phospholipids as ligands for the orphan nuclear receptor steroidogenic factor-1.
Mol.Cell, 17:491-502, 2005

PubMed Abstract: 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 angstroms 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 (approximately 1600 angstroms3), 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.

PubMed: 15721253
DOI: 10.1016/j.molcel.2005.02.002

Experimental method

X-RAY DIFFRACTION (1.5 Å)