THREE-DIMENSIONAL QUATERNARY STRUCTURE OF THE INSULIN RECEPTOR

摘要

The 3D structure of the intrinsically dimeric insulin receptor (IR) bound to its ligand, insulin, was determined by electron cryomicroscopy. Insulin labeled with gold served to locate the insulin-binding domain on the 3D structure. The 3D structure was then fitted with available known high resolution domain substructures to obtain a detailed contiguous model for this heterotetrameric (.alpha..beta.)2 transmembrane receptor. The 3D reconstruction shows that the two a subunits jointly participate in insulin binding and that the two .beta.-subunit kinases in this receptor-ligand complex are in a juxtaposition that permits traps-autophosphorylation of key tyrosine residues in the first step of insulin receptor activation.