Quaternary Structure of the Insulin-Insulin Receptor Complex

Abstract

The three-dimensional (3D) structure of the intrinsically dimeric insulin receptor bound to its ligand, insulin, was determined by electron cryomicroscopy. Gold-labeled insulin served to locate the insulin-binding domain. The 3D structure was then fitted with available known high-resolution domain substructures to obtain a detailed contiguous model for this heterotetrameric transmembrane receptor. The 3D reconstruction indicates that the two α subunits jointly participate in insulin binding and that the kinase domains in the two β subunits are in a juxtaposition that permits autophosphorylation of tyrosine residues in the first step of insulin receptor activation.