Intrinsic Disorder of the C-Terminal Domain of Drosophila Methoprene-Tolerant Protein
- Publisher: Public Library of Science
(issn: 1932-6203, eissn: 1932-6203)
Molecular Biology | Animal Models | Research Article | Molecular Biology Assays and Analysis Techniques | Transcription Factors | Amino Acid Analysis | Drosophila Melanogaster | Regulatory Proteins | Small-Angle Scattering | Protein Structure | Genetics | Physical Sciences | Proteins | Molecular Biology Techniques | Physics | Animals | Macromolecular Structure Analysis | Globular Proteins | DNA-binding proteins | Biology and Life Sciences | Research and Analysis Methods | Arthropoda | Insects | Scattering | Model Organisms | Drosophila | Gene Regulation | Biochemistry | Organisms | Intrinsically Disordered Proteins | Invertebrates | Gene Expression
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.