Brzozowski, Andrzej Marek orcid.org/0000-0001-7426-8948 (2018) Structures of insect Imp-L2 suggest an alternative strategy for regulating the bioavailability of insulin-like hormones. Nature Communications. 3860 (2018). ISSN 2041-1723
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.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © The Author(s) 2018 |
Dates: |
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Institution: | The University of York |
Academic Units: | The University of York > Faculty of Sciences (York) > Chemistry (York) |
Depositing User: | Pure (York) |
Date Deposited: | 24 Sep 2018 15:40 |
Last Modified: | 16 Oct 2024 15:07 |
Published Version: | https://doi.org/10.1038/s41467-018-06192-3 |
Status: | Published |
Refereed: | Yes |
Identification Number: | 10.1038/s41467-018-06192-3 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:136126 |