The intrinsically disordered region of GCE protein adopts a more fixed structure by interacting with the LBD of the nuclear receptor FTZ-F1
Abstract The Drosophila melanogaster Germ cell-expressed protein (GCE) is a paralog of the juvenile hormone (JH) receptor - Methoprene tolerant protein (MET). Both proteins mediate JH function, preventing precocious differentiation during D. melanogaster development. Despite that GCE and MET are oft...
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| Format: | Article |
| Language: | English |
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BMC
2020-11-01
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| Series: | Cell Communication and Signaling |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12964-020-00662-2 |
| _version_ | 1819212909468712960 |
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| author | Marta Kolonko Dominika Bystranowska Michał Taube Maciej Kozak Mark Bostock Grzegorz Popowicz Andrzej Ożyhar Beata Greb-Markiewicz |
| author_facet | Marta Kolonko Dominika Bystranowska Michał Taube Maciej Kozak Mark Bostock Grzegorz Popowicz Andrzej Ożyhar Beata Greb-Markiewicz |
| author_sort | Marta Kolonko |
| collection | DOAJ |
| description | Abstract The Drosophila melanogaster Germ cell-expressed protein (GCE) is a paralog of the juvenile hormone (JH) receptor - Methoprene tolerant protein (MET). Both proteins mediate JH function, preventing precocious differentiation during D. melanogaster development. Despite that GCE and MET are often referred to as equivalent JH receptors, their functions are not fully redundant and show tissue specificity. Both proteins belong to the family of bHLH-PAS transcription factors. The similarity of their primary structure is limited to defined bHLH and PAS domains, while their long C-terminal fragments (GCEC, METC) show significant differences and are expected to determine differences in GCE and MET protein activities. In this paper we present the structural characterization of GCEC as a coil-like intrinsically disordered protein (IDP) with highly elongated and asymmetric conformation. In comparison to previously characterized METC, GCEC is less compacted, contains more molecular recognition elements (MoREs) and exhibits a higher propensity for induced folding. The NMR shifts perturbation experiment and pull-down assay clearly demonstrated that the GCEC fragment is sufficient to form an interaction interface with the ligand binding domain (LBD) of the nuclear receptor Fushi Tarazu factor-1 (FTZ-F1). Significantly, these interactions can force GCEC to adopt more fixed structure that can modulate the activity, structure and functions of the full-length receptor. The discussed relation of protein functionality with the structural data of inherently disordered GCEC fragment is a novel look at this protein and contributes to a better understanding of the molecular basis of the functions of the C-terminal fragments of the bHLH-PAS family. Video abstract. |
| first_indexed | 2024-12-23T06:50:27Z |
| format | Article |
| id | doaj.art-8d8ba55493a94d818ba65dbb760cc563 |
| institution | Directory Open Access Journal |
| issn | 1478-811X |
| language | English |
| last_indexed | 2024-12-23T06:50:27Z |
| publishDate | 2020-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Cell Communication and Signaling |
| spelling | doaj.art-8d8ba55493a94d818ba65dbb760cc5632022-12-21T17:56:27ZengBMCCell Communication and Signaling1478-811X2020-11-0118112210.1186/s12964-020-00662-2The intrinsically disordered region of GCE protein adopts a more fixed structure by interacting with the LBD of the nuclear receptor FTZ-F1Marta Kolonko0Dominika Bystranowska1Michał Taube2Maciej Kozak3Mark Bostock4Grzegorz Popowicz5Andrzej Ożyhar6Beata Greb-Markiewicz7Department of Biochemistry, Molecular Biology and Biotechnology, Faculty of Chemistry, |Wroclaw University of Science and Technology|Department of Biochemistry, Molecular Biology and Biotechnology, Faculty of Chemistry, |Wroclaw University of Science and Technology|Department of Macromolecular Physics, Faculty of Physics, Adam Mickiewicz UniversityDepartment of Macromolecular Physics, Faculty of Physics, Adam Mickiewicz UniversityBiomolecular NMR and Center for Integrated Protein Science Munich at Department Chemie, Technical University of MunichBiomolecular NMR and Center for Integrated Protein Science Munich at Department Chemie, Technical University of MunichDepartment of Biochemistry, Molecular Biology and Biotechnology, Faculty of Chemistry, |Wroclaw University of Science and Technology|Department of Biochemistry, Molecular Biology and Biotechnology, Faculty of Chemistry, |Wroclaw University of Science and Technology|Abstract The Drosophila melanogaster Germ cell-expressed protein (GCE) is a paralog of the juvenile hormone (JH) receptor - Methoprene tolerant protein (MET). Both proteins mediate JH function, preventing precocious differentiation during D. melanogaster development. Despite that GCE and MET are often referred to as equivalent JH receptors, their functions are not fully redundant and show tissue specificity. Both proteins belong to the family of bHLH-PAS transcription factors. The similarity of their primary structure is limited to defined bHLH and PAS domains, while their long C-terminal fragments (GCEC, METC) show significant differences and are expected to determine differences in GCE and MET protein activities. In this paper we present the structural characterization of GCEC as a coil-like intrinsically disordered protein (IDP) with highly elongated and asymmetric conformation. In comparison to previously characterized METC, GCEC is less compacted, contains more molecular recognition elements (MoREs) and exhibits a higher propensity for induced folding. The NMR shifts perturbation experiment and pull-down assay clearly demonstrated that the GCEC fragment is sufficient to form an interaction interface with the ligand binding domain (LBD) of the nuclear receptor Fushi Tarazu factor-1 (FTZ-F1). Significantly, these interactions can force GCEC to adopt more fixed structure that can modulate the activity, structure and functions of the full-length receptor. The discussed relation of protein functionality with the structural data of inherently disordered GCEC fragment is a novel look at this protein and contributes to a better understanding of the molecular basis of the functions of the C-terminal fragments of the bHLH-PAS family. Video abstract.http://link.springer.com/article/10.1186/s12964-020-00662-2Germ cell-expressed proteinIntrinsically disordered proteinsbHLH-PAS transcription factorC-terminusProtein-protein interactionsFTZ-F1 |
| spellingShingle | Marta Kolonko Dominika Bystranowska Michał Taube Maciej Kozak Mark Bostock Grzegorz Popowicz Andrzej Ożyhar Beata Greb-Markiewicz The intrinsically disordered region of GCE protein adopts a more fixed structure by interacting with the LBD of the nuclear receptor FTZ-F1 Cell Communication and Signaling Germ cell-expressed protein Intrinsically disordered proteins bHLH-PAS transcription factor C-terminus Protein-protein interactions FTZ-F1 |
| title | The intrinsically disordered region of GCE protein adopts a more fixed structure by interacting with the LBD of the nuclear receptor FTZ-F1 |
| title_full | The intrinsically disordered region of GCE protein adopts a more fixed structure by interacting with the LBD of the nuclear receptor FTZ-F1 |
| title_fullStr | The intrinsically disordered region of GCE protein adopts a more fixed structure by interacting with the LBD of the nuclear receptor FTZ-F1 |
| title_full_unstemmed | The intrinsically disordered region of GCE protein adopts a more fixed structure by interacting with the LBD of the nuclear receptor FTZ-F1 |
| title_short | The intrinsically disordered region of GCE protein adopts a more fixed structure by interacting with the LBD of the nuclear receptor FTZ-F1 |
| title_sort | intrinsically disordered region of gce protein adopts a more fixed structure by interacting with the lbd of the nuclear receptor ftz f1 |
| topic | Germ cell-expressed protein Intrinsically disordered proteins bHLH-PAS transcription factor C-terminus Protein-protein interactions FTZ-F1 |
| url | http://link.springer.com/article/10.1186/s12964-020-00662-2 |
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