Figure 2.

An international structural team. (A) Steiner’s office at the University of Chicago with Oxford model of insulin in its classical crystallographic conformation (foreground). Inset at top right, Hodgkin and Steiner with matching molecular models. (B,C) Next structural frontier: the tandem hormone-binding site of the insulin receptor. (B) Domain organization of the disulfide-bridged αβ monomer (left) and ectodomain (right), comprising (αβ_Δ)₂ dimer wherein β_Δ represents a fragment lacking transmembrane α-helix and intracellular domains. L1 and αCT are highlighted in green and red (left), respectively. Domains (gray scale) are otherwise designated cysteine-rich (CR), second Leu-rich repeat domain (L2), type III fibronectin-homology domains (Fn1-3), insert domain (Ins, split between C-terminus of α subunit (bottom) and N-terminus of β subunit (top)), transmembrane and juxtamembrane regions (TM/JM), tyrosine kinase (TK), and C-terminal segment (αCT; 704-FEDYLHNVVFV-715; α-helix bold). Disulfide bridges are shown as horizontal lines. (C) Crystal structure of ectodomain. One αβ_Δ protomer is shown as a ribbon; the other as sticks. L1 and αCT in each protomer are highlighted in green and red. Electron density of ID-N is incomplete. This figure was adopted with permission from Whittaker (6). Coordinates of the ectodomain of the insulin receptor were obtained from Protein Databank entry 3LOH as described (7).