Quaternary structure of the insulin-insulin receptor complex

The three-dimensional (3D) structure of the intrinsically dimeric insulin r eceptor bound to its ligand, insulin, was determined by electron cryomicros copy. Gold-labeled insulin served to locate the insulin-binding domain. The 3D structure was then fitted with available known high-resolution domain s ubstructures to obtain a detailed contiguous model for this heterotetrameri c transmembrane receptor. The 3D reconstruction indicates that the two alph a subunits jointly participate in insulin binding and that the kinase domai ns in the two beta subunits are in a juxtaposition that permits autophospho rylation of tyrosine residues in the first step of insulin receptor activat ion.