Structural conservation of insulin/IGF signalling axis at the insulin receptors level in Drosophila and humans
Open accessPublished version of a preprint
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.
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Highly accurate protein structure prediction with AlphaFold
Jumper, J., Evans, R., Pritzel, A., Green, T., Figurnov, M., Ronneberger, O., Tunyasuvunakool, K., Bates, R., Žídek, A., Potapenko, A., et al. (2021) · Nature · doi:10.1038/s41586-021-03819-2 · Cited by 43,764 · see citing works
Insulin signaling in health and disease
White, M. F. (2003) · Science · doi:10.1126/science.1092952 · Cited by 733 · cited 1× · see citing works
“Ultimately, insulin and IGFs transduce their signals through closely related cell-surface tyrosine kinase type (RTK) insulin and IGF1 receptors, and through their hybrid dimers (Adams et al, 2000; De Meyts & Whittaker, 2002; Denley et al., 2005; Siddle, 2012; De Meyts, 2016; Saltiel, 2021; Nagao et al., 2022) (Fig.”
Insulin and its receptor: structure, function and evolution
De Meyts, P. (2004) · BioEssays · doi:10.1002/bies.20151 · Cited by 345 · see citing works
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- Authors
- Viola, C. M., Frittmann, O., Jenkins, H. T., Shafi, T., De Meyts, P., & Brzozowski, A. M.
- Affiliations
- University of York (GB)
- University Medical Center Groningen (NL)
- Corresponding author
- Brzozowski, Andrzej M.
- ORCID
- Venue
- Nature Communications
- Published
- 2023-10-07
- Volume
- 14
- Issue
- 1
- Pages
- 6271-6271
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC10560217
- OpenAlex
- W4387426226
- Cited by
- 34
- References
- 3
- Citations by year
- 2026: 10 · 2025: 15 · 2024: 6 · 2023: 3
- FWCI
- 3.00
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- Research Square (acceptedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion, cc-by)
- White Rose Research Online (University of Leeds, The University of Sheffield, University of York) (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Digital Access to Libraries (submittedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- RCUK | Medical Research Council (MR/R009066/1)
- RCUK | Biotechnology and Biological Sciences Research Council (BB/W003783/1)
- Research Councils UK (BI28576)
- Novo Nordisk (GG Dodson Fund)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurobiology and Insect Physiology Research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
- Keywords
- insulin signaling, insulin receptor, insulin-like growth factor, insulin-like peptides, receptor conformation, evolutionary conservation, IGF-1 receptor, cryo-EM structure
- MeSH terms
- Animals, Drosophila, Humans, Insulin, Insulin-Like Growth Factor I, Longevity, Receptor, Insulin, Somatomedins
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