Visualization of ligand-induced transmembrane signaling in the full-length human insulin receptor
Insulin receptor (IR) signaling plays a critical role in the regulation of metabolism and growth in multicellular organisms. IRs are unique among receptor tyrosine kinases in that they exist exclusively as covalent (αβ) homodimers at the cell surface. Transmembrane signaling by the IR can therefore...
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| Veröffentlicht in: | The Journal of cell biology 2018-05, Vol.217 (5), p.1643-1649 |
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| container_title | The Journal of cell biology |
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| creator | Gutmann, Theresia Kim, Kelly H Grzybek, Michal Walz, Thomas Coskun, Ünal |
| description | Insulin receptor (IR) signaling plays a critical role in the regulation of metabolism and growth in multicellular organisms. IRs are unique among receptor tyrosine kinases in that they exist exclusively as covalent (αβ)
homodimers at the cell surface. Transmembrane signaling by the IR can therefore not be based on ligand-induced dimerization as such but must involve structural changes within the existing receptor dimer. In this study, using glycosylated full-length human IR reconstituted into lipid nanodiscs, we show by single-particle electron microscopy that insulin binding to the dimeric receptor converts its ectodomain from an inverted U-shaped conformation to a T-shaped conformation. This structural rearrangement of the ectodomain propagates to the transmembrane domains, which are well separated in the inactive conformation but come close together upon insulin binding, facilitating autophosphorylation of the cytoplasmic kinase domains. |
| doi_str_mv | 10.1083/jcb.201711047 |
| format | Article |
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| source | Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Binding Cell growth Cell surface Cytoplasm Dimerization Dimers Electron microscopy Insulin Kinases Ligands Lipids Metabolism Signaling T shape Transmembrane domains Tyrosine |
| title | Visualization of ligand-induced transmembrane signaling in the full-length human insulin receptor |
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