Insulin receptor

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spinqualitylabelsall models Structure of human insulin receptor tyrosine kinase catalytic domain complex with insulin receptor substrate 2 peptide (cyan), Mg+2 ion (green) and ATP (PDB entry 3bu5) Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image Contents 1 Function 2 Disease 3 Structural highlights 4 3D structures of insulin receptor Function Insulin receptor (IR) is a transmembrane receptor activated by insulin, insulin-like growth factor I and II[1]. The IR is a dimer where each monomer contains 8 distinct domains. Residues 28-337 are the L1-CR domain. The β-chain contains a tyrosine kinase catalytic domain (TK) residues 1005-1310. For more details see Student Projects for UMass Chemistry 423 Spring 2012-1. Disease IR is important for the regulation of glucose homeostasis and its malfunction can cause diabetes and cancer. IR is overexpressed in cancer[2]. Structural highlights (PDB entry 3bu5). TK domain of IR contains an activation loop and a catalytic loop and . The bound IR substrate 2 peptide tyrosine is the phosphorylated residue[3]. In type 2 diabetes, the TK domain is thought to be down-regulated through phosphorylation of by protein kinease C[4]. . Water molecules shown as red spheres. See also Insulin Receptor - kinase domain (Hebrew) and Insulin receptor (Hebrew). 3D structures of insulin receptor Insulin receptor 3D structures

3D structures of insulin receptor

Updated on 29-August-2019

References

1. ↑ Lee J, Pilch PF. The insulin receptor: structure, function, and signaling. Am J Physiol. 1994 Feb;266(2 Pt 1):C319-34. PMID:8141246
2. ↑ Frasca F, Pandini G, Sciacca L, Pezzino V, Squatrito S, Belfiore A, Vigneri R. The role of insulin receptors and IGF-I receptors in cancer and other diseases. Arch Physiol Biochem. 2008 Feb;114(1):23-37. doi: 10.1080/13813450801969715 . PMID:18465356 doi:http://dx.doi.org/10.1080/13813450801969715
3. ↑ Wu J, Tseng YD, Xu CF, Neubert TA, White MF, Hubbard SR. Structural and biochemical characterization of the KRLB region in insulin receptor substrate-2. Nat Struct Mol Biol. 2008 Mar;15(3):251-8. Epub 2008 Feb 17. PMID:18278056 doi:10.1038/nsmb.1388
4. ↑ Petersen MC, Madiraju AK, Gassaway BM, Marcel M, Nasiri AR, Butrico G, Marcucci MJ, Zhang D, Abulizi A, Zhang XM, Philbrick W, Hubbard SR, Jurczak MJ, Samuel VT, Rinehart J, Shulman GI. Insulin receptor Thr1160 phosphorylation mediates lipid-induced hepatic insulin resistance. J Clin Invest. 2016 Nov 1;126(11):4361-4371. doi: 10.1172/JCI86013. Epub 2016 Oct, 17. PMID:27760050 doi:http://dx.doi.org/10.1172/JCI86013
5. ↑ Scapin G, Dandey VP, Zhang Z, Prosise W, Hruza A, Kelly T, Mayhood T, Strickland C, Potter CS, Carragher B. Structure of the Insulin Receptor-Insulin Complex by Single Particle CryoEM analysis. Nature. 2018 Feb 28. pii: nature26153. doi: 10.1038/nature26153. PMID:29512653 doi:http://dx.doi.org/10.1038/nature26153
6. ↑ Weis F, Menting JG, Margetts MB, Chan SJ, Xu Y, Tennagels N, Wohlfart P, Langer T, Muller CW, Dreyer MK, Lawrence MC. The signalling conformation of the insulin receptor ectodomain. Nat Commun. 2018 Oct 24;9(1):4420. doi: 10.1038/s41467-018-06826-6. PMID:30356040 doi:http://dx.doi.org/10.1038/s41467-018-06826-6