title: The Drosophila nuclear receptor e75 contains heme and is gas responsive.
abstract: Nuclear 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.
authors.affiliation: Banting and Best Department of Medical Research, Charles H. Best Institute, 112 College Street, Toronto, Ontario, M5G 1L6, Canada.
authors.forename: Jeff
authors.initials: J
authors.lastname: Reinking
authors.forename: Mandy M S
authors.initials: MM
authors.lastname: Lam
authors.forename: Keith
authors.initials: K
authors.lastname: Pardee
authors.forename: Heidi M
authors.initials: HM
authors.lastname: Sampson
authors.forename: Suya
authors.initials: S
authors.lastname: Liu
authors.forename: Ping
authors.initials: P
authors.lastname: Yang
authors.forename: Shawn
authors.initials: S
authors.lastname: Williams
authors.forename: Wendy
authors.initials: W
authors.lastname: White
authors.forename: Gilles
authors.initials: G
authors.lastname: Lajoie
authors.forename: Aled
authors.initials: A
authors.lastname: Edwards
authors.forename: Henry M
authors.initials: HM
authors.lastname: Krause
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002248:Carbon Monoxide / Q000378:metabolism*; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism*; D019281:Dimerization; D029721:Drosophila Proteins / Q000378:metabolism; D004331:Drosophila melanogaster / Q000166:cytology / Q000378:metabolism*; D006418:Heme / Q000378:metabolism*; D006801:Humans; D019476:Insect Proteins / Q000378:metabolism*; D008024:Ligands; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009569:Nitric Oxide / Q000378:metabolism*; D010084:Oxidation-Reduction; D011485:Protein Binding; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D011987:Receptors, Steroid / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; C087173:E75 protein, insect; C106186:Hr3 protein, Drosophila; D019476:Insect Proteins; D008024:Ligands; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D009569:Nitric Oxide; D006418:Heme; D002248:Carbon Monoxide