'''The Crystal Structure of Human Liver Receptor Homologue-1'''
===The Crystal Structure of Human Liver Receptor Homologue-1===
==Overview==
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Steroidogenic factor-1 (SF-1) and liver receptor homologue-1 (LRH-1) belong to the fushi tarazu factor 1 subfamily of nuclear receptors. SF-1 is an essential factor for sex determination during development and regulates adrenal and gonadal steroidogenesis in the adult, whereas LRH-1 is a critical factor for development of endodermal tissues and regulates cholesterol and bile acid homeostasis. Regulatory ligands are unknown for SF-1 and LRH-1. A reported mouse LRH-1 structure revealed an empty pocket in a region commonly occupied by ligands in the structures of other nuclear receptors, and pocket-filling mutations did not alter the constitutive activity observed. Here we report the crystal structures of the putative ligand-binding domains of human SF-1 at 2.1-A resolution and human LRH-1 at 2.5-A resolution. Both structures bind a coactivator-derived peptide at the canonical activation-function surface, thus adopting the transcriptionally activating conformation. In human LRH-1, coactivator peptide binding also occurs to a second site. We discovered in both structures a phospholipid molecule bound in a pocket of the putative ligand-binding domain. MS analysis of the protein samples used for crystallization indicated that the two proteins associate with a range of phospholipids. Mutations of the pocket-lining residues reduced the transcriptional activities of SF-1 and LRH-1 in mammalian cell transfection assays without affecting their expression levels. These results suggest that human SF-1 and LRH-1 may be ligand-binding receptors, although it remains to be seen if phospholipids or possibly other molecules regulate SF-1 or LRH-1 under physiological conditions.
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==About this Structure==
==About this Structure==
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[[Category: Phosphatidylethanolamine]]
[[Category: Phosphatidylethanolamine]]
[[Category: Phospholipid]]
[[Category: Phospholipid]]
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Revision as of 03:31, 29 July 2008
This article has been automatically seeded. Changes to this page should pertain to the PDB entry only and not to the protein or biomolecule in general.
1ZDU is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
The crystal structures of human steroidogenic factor-1 and liver receptor homologue-1., Wang W, Zhang C, Marimuthu A, Krupka HI, Tabrizizad M, Shelloe R, Mehra U, Eng K, Nguyen H, Settachatgul C, Powell B, Milburn MV, West BL, Proc Natl Acad Sci U S A. 2005 May 24;102(21):7505-10. Epub 2005 May 16. PMID:15897460
