Viola, Cristina M., Frittmann, Orsolya, Jenkins, Huw T. orcid.org/0000-0002-3302-6966 et al. (3 more authors) (2023) Structural conservation of insulin/IGF signalling axis at the insulin receptors level in Drosophila and humans. Nature Communications. 6271. ISSN 2041-1723
Abstract
The insulin-related hormones regulate key life processes in Metazoa, from metabolism to growth, lifespan and aging, through an evolutionarily conserved insulin signalling axis (IIS). In humans the IIS axis is controlled by insulin, two insulin-like growth factors, two isoforms of the insulin receptor (hIR-A and -B), and its homologous IGF-1R. In Drosophila, this signalling engages seven insulin-like hormones (DILP1-7) and a single receptor (dmIR). This report describes the cryoEM structure of the dmIR ectodomain:DILP5 complex, revealing high structural homology between dmIR and hIR. The excess of DILP5 yields dmIR complex in an asymmetric 'T' conformation, similar to that observed in some complexes of human IRs. However, dmIR binds three DILP5 molecules in a distinct arrangement, showing also dmIR-specific features. This work adds structural support to evolutionary conservation of the IIS axis at the IR level, and also underpins a better understanding of an important model organism.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © The Author(s) 2023 |
Dates: |
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Institution: | The University of York |
Academic Units: | The University of York > Faculty of Sciences (York) > Centre for Immunology and Infection (CII) (York) The University of York > Faculty of Sciences (York) > Hull York Medical School (York) The University of York > Faculty of Sciences (York) > Chemistry (York) |
Depositing User: | Pure (York) |
Date Deposited: | 18 Oct 2023 12:00 |
Last Modified: | 16 Oct 2024 19:32 |
Published Version: | https://doi.org/10.1038/s41467-023-41862-x |
Status: | Published |
Refereed: | Yes |
Identification Number: | 10.1038/s41467-023-41862-x |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:204366 |
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Filename: s41467_023_41862_x.pdf
Description: Structural conservation of insulin/IGF signalling axis at the insulin receptors level in Drosophila and humans
Licence: CC-BY 2.5