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

Using glycosylated full-length human insulin receptor reconstituted into lipid nanodiscs, we show that insulin binding to the dimeric receptor converts its ectodomains from an inverted U-shaped to a T-shaped conformation. This unprecedented structural rearrangement of the ectodomains propagates to the transmembrane domains, which are well separated in the inactive conformation, but come together upon insulin binding, allowing autophosphorylation of the cytoplasmic kinase domains.