The Drosophila Nuclear Receptor E75 Contains Heme and Is Gas Responsive
| Autor: | Ping Yang, Keith Pardee, Heidi M. Sampson, Mandy M.S. Lam, Wendy White, Suya Liu, Shawn P. Williams, Jeff Reinking, Aled M. Edwards, Gilles A. Lajoie, Henry M. Krause |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Receptors
Steroid Transcription Genetic Molecular Sequence Data Receptors Cytoplasmic and Nuclear Heme Plasma protein binding Ligands Nitric Oxide DNA-binding protein General Biochemistry Genetics and Molecular Biology Cofactor Cell Line 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Animals Drosophila Proteins Humans Amino Acid Sequence Binding site Transcription factor 030304 developmental biology Carbon Monoxide 0303 health sciences Binding Sites biology Biochemistry Genetics and Molecular Biology(all) DNA-Binding Proteins Drosophila melanogaster Biochemistry chemistry Nuclear receptor Mutagenesis Site-Directed biology.protein Biophysics Insect Proteins Dimerization Oxidation-Reduction 030217 neurology & neurosurgery Drosophila Protein Protein Binding |
| Zdroj: | Cell. 122:195-207 |
| ISSN: | 0092-8674 |
| Popis: | SummaryNuclear receptors are a family of transcription factors with structurally conserved ligand binding domains that regulate their activity. Despite intensive efforts to identify ligands, most nuclear receptors are still “orphans.” Here, we demonstrate that the ligand binding pocket of the Drosophila nuclear receptor E75 contains a heme prosthetic group. E75 absorption spectra, resistance to denaturants, and effects of site-directed mutagenesis indicate a single, coordinately bound heme molecule. A correlation between the levels of E75 expression and the levels of available heme suggest a possible role as a heme sensor. The oxidation state of the heme iron also determines whether E75 can interact with its heterodimer partner DHR3, suggesting an additional role as a redox sensor. Further, the E75-DHR3 interaction is also regulated by the binding of NO or CO to the heme center, suggesting that E75 may also function as a diatomic gas sensor. Possible mechanisms and roles for these interactions are discussed. |
| Databáze: | OpenAIRE |
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