| Structural highlights
Function
INSR_DROME Has a ligand-stimulated tyrosine-protein kinase activity. Required for cell survival. Regulates body size and organ size by altering cell number and cell size in a cell-autonomous manner. Involved in the development of the embryonic nervous system, and is necessary for axon guidance and targeting in the visual system. Also plays a role in life-span determination.[1] [2] [3] [4] [5] [6]
Publication Abstract from PubMed
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.
Structural conservation of insulin/IGF signalling axis at the insulin receptors level in Drosophila and humans.,Viola CM, Frittmann O, Jenkins HT, Shafi T, De Meyts P, Brzozowski AM Nat Commun. 2023 Oct 7;14(1):6271. doi: 10.1038/s41467-023-41862-x. PMID:37805602[7]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Marin-Hincapie M, Garofalo RS. The carboxyl terminal extension of the Drosophila insulin receptor homologue binds IRS-1 and influences cell survival. J Biol Chem. 1999 Aug 27;274(35):24987-94. PMID:10455177 doi:10.1074/jbc.274.35.24987
- ↑ Brogiolo W, Stocker H, Ikeya T, Rintelen F, Fernandez R, Hafen E. An evolutionarily conserved function of the Drosophila insulin receptor and insulin-like peptides in growth control. Curr Biol. 2001 Feb 20;11(4):213-21. PMID:11250149 doi:10.1016/s0960-9822(01)00068-9
- ↑ Tatar M, Kopelman A, Epstein D, Tu MP, Yin CM, Garofalo RS. A mutant Drosophila insulin receptor homolog that extends life-span and impairs neuroendocrine function. Science. 2001 Apr 6;292(5514):107-10. PMID:11292875 doi:10.1126/science.1057987
- ↑ Song J, Wu L, Chen Z, Kohanski RA, Pick L. Axons guided by insulin receptor in Drosophila visual system. Science. 2003 Apr 18;300(5618):502-5. PMID:12702880 doi:10.1126/science.1081203
- ↑ Fernandez R, Tabarini D, Azpiazu N, Frasch M, Schlessinger J. The Drosophila insulin receptor homolog: a gene essential for embryonic development encodes two receptor isoforms with different signaling potential. EMBO J. 1995 Jul 17;14(14):3373-84. PMID:7628438 doi:10.1002/j.1460-2075.1995.tb07343.x
- ↑ Chen C, Jack J, Garofalo RS. The Drosophila insulin receptor is required for normal growth. Endocrinology. 1996 Mar;137(3):846-56. PMID:8603594 doi:10.1210/endo.137.3.8603594
- ↑ Viola CM, Frittmann O, Jenkins HT, Shafi T, De Meyts P, Brzozowski AM. Structural conservation of insulin/IGF signalling axis at the insulin receptors level in Drosophila and humans. Nat Commun. 2023 Oct 7;14(1):6271. PMID:37805602 doi:10.1038/s41467-023-41862-x
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