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

Mark Bostock¹  Grzegorz Popowicz¹  Dominika Bystranowska²  Andrzej Ożyhar²  Marta Kolonko²  Beata Greb-Markiewicz²  Michał Taube³  Maciej Kozak⁴ 

[1] Biomolecular NMR and Center for Integrated Protein Science Munich at Department Chemie, Technical University of Munich, Lichtenbergstraße 4, 85748, Garching, Germany;Institute of Structural Biology, Helmholtz Zentrum München, Ingolstädter Landstraße 1, 85764, Oberschleißheim, Germany;Department of Biochemistry, Molecular Biology and Biotechnology, Faculty of Chemistry,

[2] Wroclaw University of Science and Technology

[3] , Wybrzeze Wyspianskiego 27, 50-370, Wroclaw, Poland;Department of Macromolecular Physics, Faculty of Physics, Adam Mickiewicz University, Uniwersytetu Poznanskiego 2, 61-614, Poznan, Poland;Department of Macromolecular Physics, Faculty of Physics, Adam Mickiewicz University, Uniwersytetu Poznanskiego 2, 61-614, Poznan, Poland;National Synchrotron Radiation Centre SOLARIS, Jagiellonian University, Czerwone Maki 98, 30-392, Krakow, Poland;

关键词: Germ cell-expressed protein;    Intrinsically disordered proteins;    bHLH-PAS transcription factor;    C-terminus;    Protein-protein interactions;    FTZ-F1;   

DOI  :  10.1186/s12964-020-00662-2

来源: Springer

【 摘 要 】

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.Bgj8xxK93U2keSEUSbLjSCVideo abstract.

【 授权许可】

CC BY