Abstract
The Drosophila melanogaster Germcell-expressed protein (GCE) is a paralog of the juvenile hormone (JH) receptor -Methoprene tolerant protein (MET). Both proteins mediate JH function, preventingprecocious differentiation during D. melanogasterdevelopment. Despite that GCE and MET are often referred to as equivalent JHreceptors, their functions are not fully redundant and show tissue specificity. Bothproteins belong to the family of bHLH-PAS transcription factors. The similarity oftheir primary structure is limited to defined bHLH and PAS domains, while their longC-terminal fragments (GCEC, METC) show significant differences and are expected todetermine differences in GCE and MET protein activities. In this paper we presentthe structural characterization of GCEC as a coil-like intrinsically disorderedprotein (IDP) with highly elongated and asymmetric conformation. In comparison topreviously characterized METC, GCEC is less compacted, contains more molecularrecognition elements (MoREs) and exhibits a higher propensity for induced folding.The NMR shifts perturbation experiment and pull-down assay clearly demonstrated thatthe GCEC fragment is sufficient to form an interaction interface with the ligandbinding domain (LBD) of the nuclear receptor Fushi Tarazu factor-1 (FTZ-F1).Significantly, these interactions can force GCEC to adopt more fixed structure thatcan modulate the activity, structure and functions of the full-length receptor. Thediscussed relation of protein functionality with the structural data of inherentlydisordered GCEC fragment is a novel look at this protein and contributes to a betterunderstanding of the molecular basis of the functions of the C-terminal fragments ofthe bHLH-PAS family.2UuA8w5_5agRn7KffXMuPjVideo abstract.
Highlights
Drosophila melanogaster has become an important model organism in research aimed to understand the molecular basis of organism development, since the fundamental mechanisms and pathways controlling development have been preserved during evolution [1].Insect growth and development are controlled by the cross-talk between only two hormones: 20hydroxyecdysone (20E) and juvenile hormone (JH) [2]
Short fragments with a tendency to order occur mainly in the area near 30 aa, between 150 and 200 aa, and near 260 aa, and could participate in the protein-protein interactions (PPIs) or act as the molecular recognition elements (MoREs, indicated in red color)
In summary, we present the structural characterization of the Germ cellexpressed protein (GCE) bHLH-PAS protein Cterminal region (GCEC), referring the obtained data to the first characterized C-terminus of the paralogous protein – Methoprene tolerant protein (MET) (METC)
Summary
Drosophila melanogaster has become an important model organism in research aimed to understand the molecular basis of organism development, since the fundamental mechanisms and pathways controlling development have been preserved during evolution [1].Insect growth and development are controlled by the cross-talk between only two hormones: 20hydroxyecdysone (20E) and juvenile hormone (JH) [2]. The Methoprene tolerant protein (MET), as the JH receptor, mediates the function of JH in preventing the precocious development of D. melanogaster during metamorphosis [6]. The functional unevenness between GCE and MET as transcription factors seems to be exceptionally interesting. These proteins exhibit differentiated stage and tissue specific expression, and different functions during organism development and adulthood. It was shown that the met null-mutants of D. melanogaster are viable at the pupae stage due to the presence of GCE. The differentiated subcellular distribution of MET and GCE during D. melanogaster development could be one of the factors responsible for their partially different functions
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