The Insulin receptor plays a central role in cellular signaling. It regulates metabolism, growth, division, differentiation, and survival. Insulin resistance contributes to the pathogenesis of type 2 diabetes mellitus and the onset of Alzheimer’s disease. Customize and 3D print this Biologic Model of an Insulin Receptor bound by Insulin.
“Insulin receptor signaling has a central role in mammalian biology, regulating cellular metabolism, growth, division, differentiation, and survival. Insulin resistance contributes to the pathogenesis of type 2 diabetes mellitus and the onset of Alzheimer’s disease; aberrant signaling occurs in diverse cancers, exacerbated by cross-talk with the homologous type 1 insulin-like growth factor receptor (IGF1R). Despite more than three decades of investigation, the three-dimensional structure of the insulin-insulin receptor complex has proved elusive, confounded by the complexity of producing the receptor protein. Here we present the first view, to our knowledge, of the interaction of insulin with its primary binding site on the insulin receptor, on the basis of four crystal structures of insulin bound to truncated insulin receptor constructs. The direct interaction of insulin with the first leucine-rich-repeat domain (L1) of the insulin receptor is seen to be sparse, the hormone instead engaging the insulin receptor carboxy-terminal ?-chain (?CT) segment, which is itself remodeled on the face of L1 upon insulin binding. Contact between insulin and L1 is restricted to insulin B-chain residues. The ?CT segment displaces the B-chain C-terminal ?-strand away from the hormone core, revealing the mechanism of a long-proposed conformational switch in insulin upon receptor engagement. This mode of hormone-receptor recognition is novel within the broader family of receptor tyrosine kinases. We support these findings by photo-crosslinking data that place the suggested interactions into the context of the holoreceptor and by isothermal titration calorimetry data that dissect the hormone-insulin receptor interface. Together, our findings provide an explanation for a wealth of biochemical data from the insulin receptor and IGF1R systems relevant to the design of therapeutic insulin analogs. ”
PDB ID: 5KQV
3D Visualizations and Photos of Biologic Model, Insulin Receptor-bound by Insulin.
The Insulin Receptor printed in full-color sandstone. Receptor dimer chains colored blue and green. Insulin chains A and B colored Orange and Yellow.
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