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

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. Turkenburg; Pierre De Meyts; Andrzej M. Brzozowski

doi:10.1038/s41467-018-06192-3

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

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. Turkenburg, Pierre De Meyts, Andrzej M. Brzozowski^*

^*Corresponding author for this work

Glycomics Program

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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.

Original language	English
Article number	3860
Journal	Nature Communications
Volume	9
Number of pages	12
ISSN	2041-1723
DOIs	https://doi.org/10.1038/s41467-018-06192-3
Publication status	Published - 2018

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Structures of insect Imp-L2 suggest an alternative strategy for regulating the bioavailability of insulin-like hormonesFinal published version, 3.86 MBLicence: CC BY

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Roed, N. K., Viola, C. M., Kristensen, O., Schluckebier, G., Norrman, M., Sajid, W., Wade, J. D., Andersen, A. S., Kristensen, C., Ganderton, T. R., Turkenburg, J. P., De Meyts, P., & Brzozowski, A. M. (2018). Structures of insect Imp-L2 suggest an alternative strategy for regulating the bioavailability of insulin-like hormones. Nature Communications, 9, Article 3860. https://doi.org/10.1038/s41467-018-06192-3

Roed, NK, Viola, CM, Kristensen, O, Schluckebier, G, Norrman, M, Sajid, W, Wade, JD, Andersen, AS, Kristensen, C, Ganderton, TR, Turkenburg, JP, De Meyts, P & Brzozowski, AM 2018, 'Structures of insect Imp-L2 suggest an alternative strategy for regulating the bioavailability of insulin-like hormones', Nature Communications, vol. 9, 3860. https://doi.org/10.1038/s41467-018-06192-3

@article{5439b0539f5549ac85a446ab759f6650,

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

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.",

author = "Roed, {Nikolaj Kulahin} and Viola, {Cristina M.} and Ole Kristensen and Gerd Schluckebier and Mathias Norrman and Waseem Sajid and Wade, {John D.} and Andersen, {Asser Sloth} and Claus Kristensen and Ganderton, {Timothy R.} and Turkenburg, {Johan P.} and {De Meyts}, Pierre and Brzozowski, {Andrzej M.}",

year = "2018",

doi = "10.1038/s41467-018-06192-3",

language = "English",

volume = "9",

journal = "Nature Communications",

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T1 - Structures of insect Imp-L2 suggest an alternative strategy for regulating the bioavailability of insulin-like hormones

AU - Roed, Nikolaj Kulahin

AU - Viola, Cristina M.

AU - Kristensen, Ole

AU - Schluckebier, Gerd

AU - Norrman, Mathias

AU - Sajid, Waseem

AU - Wade, John D.

AU - Andersen, Asser Sloth

AU - Kristensen, Claus

AU - Ganderton, Timothy R.

AU - Turkenburg, Johan P.

AU - De Meyts, Pierre

AU - Brzozowski, Andrzej M.

PY - 2018

Y1 - 2018

N2 - 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.

AB - 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.

U2 - 10.1038/s41467-018-06192-3

DO - 10.1038/s41467-018-06192-3

M3 - Journal article

C2 - 30242155

AN - SCOPUS:85053733555

SN - 2041-1723

VL - 9

JO - Nature Communications

JF - Nature Communications

M1 - 3860

ER -

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

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