6pxw | pdb_00006pxw

Cryo-EM structure of full-length insulin receptor bound to 4 insulin. 3D refinement was focused on the top part of the receptor complex.

Loading... Status: waiting for Mol* initialization Structural highlights 6pxw is a 6 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.1Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function A6XGL2_HUMAN Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synthesis in liver (By similarity).[SAAS:SAAS022353_004_028339] Publication Abstract from PubMed 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 alpha-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. Activation mechanism of the insulin receptor revealed by cryo-EM structure of the fully liganded receptor-ligand complex.,Uchikawa E, Choi E, Shang G, Yu H, Bai XC Elife. 2019 Aug 22;8. pii: 48630. doi: 10.7554/eLife.48630. PMID:31436533 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Insulin receptor 3D structures

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