primary spermatocyte growth / negative regulation of peptide hormone secretion / Extra-nuclear estrogen signaling / negative regulation of entry into reproductive diapause / Insulin signaling pathway / Insulin receptor recycling / female mating behavior / response to anoxia / embryonic development via the syncytial blastoderm / male germ-line stem cell asymmetric division ...primary spermatocyte growth / negative regulation of peptide hormone secretion / Extra-nuclear estrogen signaling / negative regulation of entry into reproductive diapause / Insulin signaling pathway / Insulin receptor recycling / female mating behavior / response to anoxia / embryonic development via the syncytial blastoderm / male germ-line stem cell asymmetric division / female germ-line stem cell population maintenance / germ-band shortening / histone H2AXY142 kinase activity / carbohydrate homeostasis / germ-line stem-cell niche homeostasis / imaginal disc growth / negative regulation of circadian sleep/wake cycle, sleep / open tracheal system development / positive regulation of neuron remodeling / germ-line stem cell division / follicle cell of egg chamber development / lymph gland development / positive regulation of border follicle cell migration / female germ-line stem cell asymmetric division / positive regulation of fat cell proliferation / intestinal stem cell homeostasis / growth cone membrane / positive regulation of organ growth / histone H3Y41 kinase activity / positive regulation of lipid storage / insulin receptor complex / regulation of organ growth / positive regulation of multicellular organism growth / sleep / triglyceride homeostasis / embryo development ending in birth or egg hatching / insulin binding / positive regulation of wound healing / negative regulation of macroautophagy / negative regulation of feeding behavior / positive regulation of neuroblast proliferation / female gonad development / lipid homeostasis / insulin receptor substrate binding / regulation of multicellular organism growth / positive regulation of cell size / developmental growth / phosphatidylinositol 3-kinase binding / axon guidance / cell surface receptor protein tyrosine kinase signaling pathway / cholesterol homeostasis / cellular response to starvation / determination of adult lifespan / locomotory behavior / insulin receptor binding / response to cocaine / placental growth factor receptor activity / insulin receptor activity / hepatocyte growth factor receptor activity / macrophage colony-stimulating factor receptor activity / platelet-derived growth factor alpha-receptor activity / platelet-derived growth factor beta-receptor activity / stem cell factor receptor activity / boss receptor activity / protein tyrosine kinase collagen receptor activity / brain-derived neurotrophic factor receptor activity / transmembrane-ephrin receptor activity / GPI-linked ephrin receptor activity / epidermal growth factor receptor activity / fibroblast growth factor receptor activity / insulin-like growth factor receptor activity / receptor protein-tyrosine kinase / hormone activity / multicellular organism growth / SH3 domain binding / circadian rhythm / insulin receptor signaling pathway / glucose homeostasis / nervous system development / regulation of cell population proliferation / positive regulation of cell growth / protein autophosphorylation / protein tyrosine kinase activity / response to oxidative stress / positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / positive regulation of MAPK cascade / protein phosphorylation / receptor ligand activity / axon / positive regulation of cell population proliferation / extracellular space / extracellular region / ATP binding / metal ion binding / identical protein binding / plasma membrane Similarity search - Function
Long hematopoietin receptor, single chain family signature. / Tyrosine-protein kinase, receptor class II, conserved site / Receptor tyrosine kinase class II signature. / Insulin family / Insulin-like / Insulin/IGF/Relaxin family / Insulin / insulin-like growth factor / relaxin family. / Insulin, conserved site / Insulin family signature. / Insulin-like superfamily ...Long hematopoietin receptor, single chain family signature. / Tyrosine-protein kinase, receptor class II, conserved site / Receptor tyrosine kinase class II signature. / Insulin family / Insulin-like / Insulin/IGF/Relaxin family / Insulin / insulin-like growth factor / relaxin family. / Insulin, conserved site / Insulin family signature. / Insulin-like superfamily / Receptor L-domain / Furin-like cysteine-rich domain / Receptor L-domain superfamily / Furin-like cysteine rich region / Receptor L domain / Furin-like repeat / Furin-like repeats / Growth factor receptor cysteine-rich domain superfamily / Fibronectin type III domain / : / Fibronectin type 3 domain / Fibronectin type-III domain profile. / Fibronectin type III / Fibronectin type III superfamily / Tyrosine-protein kinase, catalytic domain / Tyrosine kinase, catalytic domain / Tyrosine protein kinases specific active-site signature. / Tyrosine-protein kinase, active site / Serine-threonine/tyrosine-protein kinase, catalytic domain / Protein tyrosine and serine/threonine kinase / Protein kinase, ATP binding site / Protein kinases ATP-binding region signature. / Immunoglobulin-like fold / Protein kinase domain profile. / Protein kinase domain / Protein kinase-like domain superfamily Similarity search - Domain/homology
Biotechnology and Biological Sciences Research Council (BBSRC)
BB/W003783/1
United Kingdom
Citation
Journal: Nat Commun / Year: 2023 Title: Structural conservation of insulin/IGF signalling axis at the insulin receptors level in Drosophila and humans. Authors: Cristina M Viola / Orsolya Frittmann / Huw T Jenkins / Talha Shafi / Pierre De Meyts / Andrzej M Brzozowski / 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 ...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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