title: Intrinsic Disorder of the C-Terminal Domain of Drosophila Methoprene-Tolerant Protein.
abstract: Methoprene tolerant protein (Met) has recently been confirmed as the long-sought juvenile hormone (JH) receptor. This protein plays a significant role in the cross-talk of the 20-hydroxyecdysone (20E) and JH signalling pathways, which are important for control of insect development and maturation. Met belongs to the basic helix-loop-helix/Per-Arnt-Sim (bHLH-PAS) family of transcription factors. In these proteins, bHLH domains are typically responsible for DNA binding and dimerization, whereas the PAS domains are crucial for the choice of dimerization partner and the specificity of target gene activation. The C-terminal region is usually responsible for the regulation of protein complex activity. The sequence of the Met C-terminal region (MetC) is not homologous to any sequence deposited in the Protein Data Bank (PDB) and has not been structurally characterized to date. In this study, we show that the MetC exhibits properties typical for an intrinsically disordered protein (IDP). The final averaged structure obtained with small angle X-ray scattering (SAXS) experiments indicates that intrinsically disordered MetC exists in an extended conformation. This extended shape and the long unfolded regions characterise proteins with high flexibility and dynamics. Therefore, we suggest that the multiplicity of conformations adopted by the disordered MetC is crucial for its activity as a biological switch modulating the cross-talk of different signalling pathways in insects.
authors.affiliation: Department of Biochemistry, Faculty of Chemistry, Wrocław University of Science and Technology, Wybrzeże Wyspiańskiego 27, 50-370, Wrocław, Poland.
authors.forename: Marta
authors.initials: M
authors.lastname: Kolonko
authors.affiliation: Department of Biochemistry, Faculty of Chemistry, Wrocław University of Science and Technology, Wybrzeże Wyspiańskiego 27, 50-370, Wrocław, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Ożga
authors.affiliation: Department of Biochemistry, Faculty of Chemistry, Wrocław University of Science and Technology, Wybrzeże Wyspiańskiego 27, 50-370, Wrocław, Poland.
authors.forename: Rafał
authors.initials: R
authors.lastname: Hołubowicz
authors.affiliation: Joint Laboratory for SAXS studies, Faculty of Physics, Adam Mickiewicz University, Umultowska 85, 61-614, Poznań, Poland.
authors.forename: Michał
authors.initials: M
authors.lastname: Taube
authors.affiliation: Joint Laboratory for SAXS studies, Faculty of Physics, Adam Mickiewicz University, Umultowska 85, 61-614, Poznań, Poland.|Department of Macromolecular Physics, Faculty of Physics, Adam Mickiewicz University, Umultowska 85, 61-614, Poznań, Poland.
authors.forename: Maciej
authors.initials: M
authors.lastname: Kozak
authors.affiliation: Department of Biochemistry, Faculty of Chemistry, Wrocław University of Science and Technology, Wybrzeże Wyspiańskiego 27, 50-370, Wrocław, Poland.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Ożyhar
authors.affiliation: Department of Biochemistry, Faculty of Chemistry, Wrocław University of Science and Technology, Wybrzeże Wyspiańskiego 27, 50-370, Wrocław, Poland.
authors.forename: Beata
authors.initials: B
authors.lastname: Greb-Markiewicz