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Gutmann, T. ; Kim, K.H.* ; Grzybek, M. ; Walz, T.* ; Coskun, Ü.

Visualization of ligand-induced transmembrane signaling in the full-length human insulin receptor.

J. Cell Biol. 217, 1643-1649 (2018)
Verlagsversion Forschungsdaten DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
ISSN (print) / ISBN 0021-9525
e-ISSN 1540-8140
Zeitschrift Journal of Cell Biology, The
Quellenangaben Band: 217, Heft: 5, Seiten: 1643-1649 Artikelnummer: , Supplement: ,
Verlag Rockefeller University Press
Begutachtungsstatus
Institut(e) Institute for Pancreatic Beta Cell Research (IPI)