title: The composite nature of the interaction between nuclear receptors EcR and DHR38.
abstract: Ecdysteroids coordinate essential biological processes in Drosophila through a complex of two nuclear receptors, the ecdysteroid receptor (EcR) and the ultraspiracle protein (Usp). Biochemical experiments have shown that, in contrast to Usp, the EcR molecule is characterized by high intramolecular plasticity. To investigate whether this plasticity is sufficient to form EcR complexes with nuclear receptors other than Usp, we studied the interaction of EcR with the DHR38 nuclear receptor. Previous in vitro experiments suggested that DHR38 can form complexes with Usp and thus disrupt Usp-EcR interaction with the specific hsp27pal response element. This article provides the experimental evidence that EcR is able to form complexes with DHR38 as well. The recombinant DNA-binding domains (DBDs) of EcR and DHR38 interact specifically on hsp27pal. However, the interaction between the receptors is not restricted to their isolated DBDs. We pre\xadsent data that indicate that the full-length EcR and DHR38 can also form specific complexes within the nuclei of living cells. This interaction is mediated by the hinge region of EcR, which was recently classified as an intrinsically disordered region. Our results indicate that DHR38 might modulate the activity of the Usp-EcR heterodimer by forming complexes with both of its components.
authors.affiliation: Department of Biochemistry, Faculty of Chemistry, Wrocław University of Technology, Wybrzeże Wyspiańskiego 27, 50-370 Wrocław, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Zoglowek
authors.forename: Marek
authors.initials: M
authors.lastname: Orłowski
authors.forename: Szymon
authors.initials: S
authors.lastname: Pakuła
authors.forename: Joanna
authors.initials: J
authors.lastname: Dutko-Gwóźdź
authors.forename: Dorota
authors.initials: D
authors.lastname: Pajdzik
authors.forename: Tomasz
authors.initials: T
authors.lastname: Gwóźdź
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Rymarczyk
authors.forename: Elżbieta
authors.initials: E
authors.lastname: Wieczorek
authors.forename: Jurek
authors.initials: J
authors.lastname: Dobrucki
authors.forename: Piotr
authors.initials: P
authors.lastname: Dobryszycki
authors.forename: Andrzej
authors.initials: A
authors.lastname: Ożyhar
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002470:Cell Survival; D004247:DNA / Q000235:genetics / Q000378:metabolism; D029721:Drosophila Proteins / Q000737:chemistry / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology / Q000378:metabolism; D055551:HSP27 Heat-Shock Proteins / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry / Q000378:metabolism*; D011987:Receptors, Steroid / Q000737:chemistry / Q000378:metabolism*; D013379:Substrate Specificity
chemical_list: D029721:Drosophila Proteins; D055551:HSP27 Heat-Shock Proteins; C095176:Hr38 protein, Drosophila; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; C034808:ecdysteroid receptor; D004247:DNA