Modular structure of the insulin receptor. Left: cartoon of the α2β2 structure of the insulin receptor, drawn to scale. On the left half of the receptor, spans of the 22 exon-encoded sequences. On the right half, spans of predicted protein modules. Orange arrowheads: N-glycosylation sites. Green arrowheads: ligand binding “hotspots” identified by single amino acids site-directed mutagenesis (see text and for details). Right: Supra-domain organisation of the insulin receptor. Stretched-out model of predicted or actual modular structures (L1CL2 and TK domains based on X-ray analysis data^110,114). The 3D structure of the insulin molecule¹⁸⁷ is also shown. The classical binding surface is shown in yellow as van der Waals spheres; A13 and B17 Leu in the new binding surface are shown in red. Modelling using DS ViewerLite 5.0 (Accelrys). Reprinted with permission from De Meyts P and Whittaker J. Nat Rev Drug Disc 2002; 1:769-783.