1zdu

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spinqualitylabelsall models 1zdu, resolution 2.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

The Crystal Structure of Human Liver Receptor Homologue-1

Overview

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.

About this Structure

1ZDU is a Protein complex structure of sequences from Homo sapiens with P3A and TRS as ligands. 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

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