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Kolonko-Adamska, M.* ; Zawadzka-Kazimierczuk, A.* ; Bartosińska-Marzec, P.* ; Koźmiński, W.* ; Popowicz, G.M. ; Krężel, A.* ; Ożyhar, A.* ; Greb-Markiewicz, B.*

Interaction patterns of methoprene-tolerant and germ cell-expressed Drosophila JH receptors suggest significant differences in their functioning.

Front. Mol. Biosci. 10:1215550 (2023)
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Methoprene-tolerant (Met) and germ cell-expressed (Gce) proteins were shown to be juvenile hormone (JH) receptors of Drosophila melanogaster with partially redundant functions. We raised the question of where the functional differentiation of paralogs comes from. Therefore, we tested Met and Gce interaction patterns with selected partners. In this study, we showed the ability of Gce and its C-terminus (GceC) to interact with 14-3-3 in the absence of JH. In contrast, Met or Met C-terminus (MetC) interactions with 14-3-3 were not observed. We also performed a detailed structural analysis of Met/Gce interactions with the nuclear receptor fushi tarazu factor-1 (Ftz-F1) ligand-binding domain. We showed that GceC comprising an Ftz-F1-binding site and full-length protein interacts with Ftz-F1. In contrast to Gce, only MetC (not full-length Met) can interact with Ftz-F1 in the absence of JH. We propose that the described differences result from the distinct tertiary structure and accessibility of binding sites in the full-length Met/Gce. Moreover, we hypothesize that each interacting partner can force disordered MetC and GceC to change the structure in a partner-specific manner. The observed interactions seem to determine the subcellular localization of Met/Gce by forcing their translocation between the nucleus and the cytoplasm, which may affect the activity of the proteins. The presented differences between Met and Gce can be crucial for their functional differentiation during D. melanogaster development and indicate Gce as a more universal and more active paralog. It is consistent with the theory indicating gce as an ancestor gene.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Drosophila Melanogaster ; Germ Cell Expressed ; Hormone Receptor ; Juvenile Hormone ; Methoprene Tolerant ; Structure–function; Juvenile-hormone Receptor; Automatic Resonance Assignment; Aryl-hydrocarbon Receptor; Bhlh-pas Family; Nuclear Receptor; Protein Interactions; Crystal-structure; Molecular Actions; Chemical-shifts; Activation
Language english
Publication Year 2023
HGF-reported in Year 2023
ISSN (print) / ISBN 2296-889X
e-ISSN 2296-889X
Journal Frontiers in Molecular Biosciences
Quellenangaben Volume: 10, Issue: , Pages: , Article Number: 1215550 Supplement: ,
Publisher Frontiers
Publishing Place Lausanne
Reviewing status Peer reviewed
Institute(s) Institute of Structural Biology (STB)
POF-Topic(s) 30203 - Molecular Targets and Therapies
Research field(s) Enabling and Novel Technologies
PSP Element(s) G-503000-001
Grants
Polish National Science Center
Polish Ministry of Science and High Education for the Faculty of Chemistry of Wroclaw University of Science and Technology
ETIUDA
Polish National Science Center: PRELUDIUM predoctoral grant
This work was supported by the Polish National Science Center: PRELUDIUM predoctoral grant UMO-2017/27/N/NZ1/01783 (MK-A) and ETIUDA doctoral scholarship UMO-2018/28/T/NZ1/00337 (MK-A) and partially supported by a subsidy from the Polish Ministry of Scien
DOI 10.3389/fmolb.2023.1215550
WOS ID 001057786400001
Scopus ID 85169317090
PubMed ID 37654797
Erfassungsdatum 2023-10-18
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