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.

中文翻译：

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GCE蛋白的内在无序区域通过与核受体FTZ-F1的LBD相互作用而采用更固定的结构

黑腹果蝇生殖细胞表达蛋白 (GCE) 是保幼激素 (JH) 受体 - 烯虫酯耐受蛋白 (MET) 的旁系同源物。这两种蛋白质都介导 JH 功能，防止黑腹果蝇发育过程中的早熟分化。尽管 GCE 和 MET 通常被称为等效的 JH 受体，但它们的功能并不完全多余，并显示出组织特异性。这两种蛋白质都属于 bHLH-PAS 转录因子家族。它们一级结构的相似性仅限于定义的 bHLH 和 PAS 结构域，而它们的长 C 端片段（GCEC、METC）显示出显着差异，预计将决定 GCE 和 MET 蛋白活性的差异。在本文中，我们将 GCEC 的结构表征描述为具有高度伸长和不对称构象的线圈状内在无序蛋白 (IDP)。与先前表征的 METC 相比，GCEC 不太紧凑，包含更多的分子识别元素 (MoRE)，并表现出更高的诱导折叠倾向。NMR 位移扰动实验和下拉分析清楚地表明，GCEC 片段足以与核受体 Fushi Tarazu 因子-1 (FTZ-F1) 的配体结合域 (LBD) 形成相互作用界面。重要的是，这些相互作用可以迫使 GCEC 采用更固定的结构，可以调节全长受体的活性、结构和功能。