7sl7

Full-length insulin receptor bound with both site 1 binding deficient mutant insulin (A-V3E) and site 2 binding deficient mutant insulin (A-L13R)

spinqualitylabelsall models 7sl7, resolution 3.10Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7sl7 is a 10 chain structure with sequence from Homo sapiens and Mus musculus. 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 Publication Abstract from PubMed Insulin receptor (IR) signaling controls multiple facets of animal physiology. Maximally four insulins bind to IR at two distinct sites, termed site-1 and site-2. However, the precise functional roles of each binding event during IR activation remain unresolved. Here, we showed that IR incompletely saturated with insulin predominantly forms an asymmetric conformation and exhibits partial activation. IR with one insulin bound adopts a Gamma-shaped conformation. IR with two insulins bound assumes a T-shaped conformation. One insulin binds at site-1 and another simultaneously contacts both site-1 and site-2 in the T-shaped IR dimer. We further show that concurrent binding of four insulins to sites-1 and -2 prevents the formation of asymmetric IR and promotes the T-shaped symmetric, fully active state. Collectively, our results demonstrate how the synergistic binding of multiple insulins promotes optimal IR activation. Synergistic activation of the insulin receptor via two distinct sites.,Li J, Park J, Mayer JP, Webb KJ, Uchikawa E, Wu J, Liu S, Zhang X, Stowell MHB, Choi E, Bai XC Nat Struct Mol Biol. 2022 Apr;29(4):357-368. doi: 10.1038/s41594-022-00750-6. , Epub 2022 Mar 31. PMID:35361965 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Insulin receptor 3D structures

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