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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.

SUBMITTER: Roed NK

PROVIDER: S-EPMC6155051 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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

Roed Nikolaj Kulahin NK Viola Cristina M CM Kristensen Ole O Schluckebier Gerd G Norrman Mathias M Sajid Waseem W Wade John D JD Andersen Asser Sloth AS Kristensen Claus C Ganderton Timothy R TR Turkenburg Johan P JP De Meyts Pierre P Brzozowski Andrzej M AM

Nature communications 20180921 1

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 stru ...[more]

PMID: 30242155

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

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

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