1yuc

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spinqualitylabelsall models 1yuc, resolution 1.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

Human Nuclear Receptor Liver Receptor Homologue-1, LRH-1, Bound to Phospholipid and a Fragment of Human SHP

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

Overview

The human nuclear receptor liver receptor homolog 1 (hLRH-1) plays an, important role in the development of breast carcinomas. This orphan, receptor is efficiently downregulated by the unusual co-repressor SHP and, has been thought to be ligand-independent. We present the crystal, structure at a resolution of 1.9 A of the ligand-binding domain of hLRH-1, in complex with the NR box 1 motif of human SHP, which we find contacts, the AF-2 region of hLRH-1 using selective structural motifs. Electron, density indicates phospholipid bound within the ligand-binding pocket, which we confirm using mass spectrometry of solvent-extracted samples. We, further show that pocket mutations reduce phospholipid binding and, receptor activity in vivo. Our results indicate that hLRH-1's control of, gene expression is mediated by phospholipid binding, and establish hLRH-1, as a novel target for compounds designed to slow breast cancer, development.

Disease

Known diseases associated with this structure: Obesity, mild, early-onset OMIM:[604630]

About this Structure

1YUC is a Protein complex structure of sequences from Homo sapiens with EPH and GOL as ligands. Full crystallographic information is available from OCA.

Reference

Modulation of human nuclear receptor LRH-1 activity by phospholipids and SHP., Ortlund EA, Lee Y, Solomon IH, Hager JM, Safi R, Choi Y, Guan Z, Tripathy A, Raetz CR, McDonnell DP, Moore DD, Redinbo MR, Nat Struct Mol Biol. 2005 Apr;12(4):357-63. Epub 2005 Feb 22. PMID:15723037

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