6PXV
Cryo-EM structure of full-length insulin receptor bound to 4 insulin. 3D refinement was focused on the extracellular region.
Summary for 6PXV
| Entry DOI | 10.2210/pdb6pxv/pdb |
| EMDB information | 20522 20523 |
| Descriptor | Insulin receptor, Insulin (2 entities in total) |
| Functional Keywords | insulin receptor, insulin, signaling protein-hormone complex, signaling protein/hormone |
| Biological source | Homo sapiens (Human) More |
| Total number of polymer chains | 6 |
| Total formula weight | 341348.74 |
| Authors | Uchikawa, E.,Choi, E.,Shang, G.J.,Yu, H.T.,Bai, X.C. (deposition date: 2019-07-27, release date: 2019-09-04, Last modification date: 2024-10-23) |
| Primary citation | Uchikawa, E.,Choi, E.,Shang, G.,Yu, H.,Bai, X.C. Activation mechanism of the insulin receptor revealed by cryo-EM structure of the fully liganded receptor-ligand complex. Elife, 8:-, 2019 Cited by PubMed Abstract: Insulin signaling controls metabolic homeostasis. Here, we report the cryo-EM structure of full-length insulin receptor (IR) and insulin complex in the active state. This structure unexpectedly reveals that maximally four insulins can bind the 'T'-shaped IR dimer at four distinct sites related by 2-fold symmetry. Insulins 1 and 1' bind to sites 1 and 1', formed by L1 of one IR protomer and α-CT and FnIII-1 of the other. Insulins 2 and 2' bind to sites 2 and 2' on FnIII-1 of each protomer. Mutagenesis and cellular assays show that both sites 1 and 2 are required for optimal insulin binding and IR activation. We further identify a homotypic FnIII-2-FnIII-2 interaction in mediating the dimerization of membrane proximal domains in the active IR dimer. Our results indicate that binding of multiple insulins at two distinct types of sites disrupts the autoinhibited apo-IR dimer and stabilizes the active dimer. PubMed: 31436533DOI: 10.7554/eLife.48630 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.2 Å) |
Structure validation
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