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Structures of insect Imp-L2 suggest an alternative strategy for regulating the bioavailability of insulin-like hormones

Author

Listed:
  • Nikolaj Kulahin Roed

    (Global Research, Novo Nordisk A/S)

  • Cristina M. Viola

    (The University of York, Heslington)

  • Ole Kristensen

    (University of Copenhagen)

  • Gerd Schluckebier

    (Global Research, Novo Nordisk A/S)

  • Mathias Norrman

    (Global Research, Novo Nordisk A/S)

  • Waseem Sajid

    (Global Research, Novo Nordisk A/S)

  • John D. Wade

    (University of Melbourne
    University of Melbourne)

  • Asser Sloth Andersen

    (Global Research, Novo Nordisk A/S)

  • Claus Kristensen

    (University of Copenhagen)

  • Timothy R. Ganderton

    (The University of York, Heslington)

  • Johan P. Turkenburg

    (The University of York, Heslington)

  • Pierre Meyts

    (Global Research, Novo Nordisk A/S
    de Duve Institute)

  • Andrzej M. Brzozowski

    (The University of York, Heslington)

Abstract

The insulin/insulin-like growth factor signalling axis is an evolutionary ancient and highly conserved hormonal system involved in the regulation of metabolism, growth and lifespan in animals. Human insulin is stored in the pancreas, while insulin-like growth factor-1 (IGF-1) is maintained in blood in complexes with IGF-binding proteins (IGFBP1–6). Insect insulin-like polypeptide binding proteins (IBPs) have been considered as IGFBP-like structural and functional homologues. Here, we report structures of the Drosophila IBP Imp-L2 in its free form and bound to Drosophila insulin-like peptide 5 and human IGF-1. Imp-L2 contains two immunoglobulin-like fold domains and its architecture is unrelated to human IGFBPs, suggesting a distinct strategy for bioavailability regulation of insulin-like hormones. Similar hormone binding modes may exist in other insect vectors, as the IBP sequences are highly conserved. Therefore, these findings may open research routes towards a rational interference of transmission of diseases such as malaria, dengue and yellow fevers.

Suggested Citation

  • Nikolaj Kulahin Roed & Cristina M. Viola & Ole Kristensen & Gerd Schluckebier & Mathias Norrman & Waseem Sajid & John D. Wade & Asser Sloth Andersen & Claus Kristensen & Timothy R. Ganderton & Johan P, 2018. "Structures of insect Imp-L2 suggest an alternative strategy for regulating the bioavailability of insulin-like hormones," Nature Communications, Nature, vol. 9(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-06192-3
    DOI: 10.1038/s41467-018-06192-3
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    Cited by:

    1. Cristina M. Viola & Orsolya Frittmann & Huw T. Jenkins & Talha Shafi & Pierre Meyts & Andrzej M. Brzozowski, 2023. "Structural conservation of insulin/IGF signalling axis at the insulin receptors level in Drosophila and humans," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    2. Yoann Saucereau & Thomas H. Wilson & Matthew C. K. Tang & Martin C. Moncrieffe & Steven W. Hardwick & Dimitri Y. Chirgadze & Sandro G. Soares & Maria Jose Marcaida & Nicholas J. Gay & Monique Gangloff, 2022. "Structure and dynamics of Toll immunoreceptor activation in the mosquito Aedes aegypti," Nature Communications, Nature, vol. 13(1), pages 1-14, December.

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