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

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

J Cell Biol

Paul Langerhans Institute Dresden, Helmholtz Zentrum München, University Hospital and Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

Published: May 2018

AI Article Synopsis

Article Abstract

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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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5940312PMC
http://dx.doi.org/10.1083/jcb.201711047DOI Listing

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