FIGURE 1 The tyrosine kinase domain of the insulin receptor is activated through autophosphorylation. (a) When the tyrosine kinase domain is inactive, the activation loop (blue) sits in the active site and none of the critical Tyr residues are phosphorylated. (b) When insulin binds the receptor, the tyrosine kinase activity phosphorylates Tyr^1,158, Tyr^1,162, and Tyr^1,163. Introducing these three phosphate groups (shown in orange) results in a 30 Å movement in the activation loop, shifting it out of the substrate-binding site, which becomes available to phosphorylate target proteins (red).