scholarly journals Faculty Opinions recommendation of Visualization of ligand-induced transmembrane signaling in the full-length human insulin receptor.

2019 ◽  
Author(s):  
M Amin Arnaout ◽  
Johannes van Agthoven
Keyword(s):  
Insulin Receptor ◽  
Human Insulin ◽  
Full Length ◽  
Transmembrane Signaling ◽  
Human Insulin Receptor

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

2017 ◽  
Author(s):  
Theresia Gutmann ◽  
Kelly H. Kim ◽  
Michal Grzybek ◽  
Thomas Walz ◽  
Ünal Coskun
Keyword(s):  
Insulin Receptor ◽  
Human Insulin ◽  
Insulin Binding ◽  
Structural Rearrangement ◽  
Transmembrane Domains ◽  
Full Length ◽  
Transmembrane Signalling ◽  
Inactive Conformation ◽  
Human Insulin Receptor ◽  
Lipid Nanodiscs

ABSTRACTUsing 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.

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

2018 ◽  
Vol 217 (5) ◽  
pp. 1643-1649 ◽  
Author(s):  
Theresia Gutmann ◽  
Kelly H. Kim ◽  
Michal Grzybek ◽  
Thomas Walz ◽  
Ünal Coskun
Keyword(s):  
Insulin Receptor ◽  
Tyrosine Kinases ◽  
Structural Changes ◽  
Critical Role ◽  
Insulin Binding ◽  
Structural Rearrangement ◽  
Full Length ◽  
Transmembrane Signaling ◽  
Human Insulin Receptor ◽  
Multicellular Organisms

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)2 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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