| Structural highlights
Disease
[INSR_HUMAN] Defects in INSR are the cause of Rabson-Mendenhall syndrome (RMS) [MIM:262190]; also known as Mendenhall syndrome. RMS is a severe insulin resistance syndrome characterized by insulin-resistant diabetes mellitus with pineal hyperplasia and somatic abnormalities. Typical features include coarse, senile-appearing facies, dental and skin abnormalities, abdominal distension, and phallic enlargement. Inheritance is autosomal recessive.[1] [2] [3] [4] [5] [6] Defects in INSR are the cause of leprechaunism (LEPRCH) [MIM:246200]; also known as Donohue syndrome. Leprechaunism represents the most severe form of insulin resistance syndrome, characterized by intrauterine and postnatal growth retardation and death in early infancy. Inheritance is autosomal recessive.[7] [8] [9] [10] [11] [12] [13] [14] [15] [16] [17] [18] [19] [20] [21] [22] [23] Defects in INSR may be associated with noninsulin-dependent diabetes mellitus (NIDDM) [MIM:125853]; also known as diabetes mellitus type 2.[24] [25] [26] Defects in INSR are the cause of familial hyperinsulinemic hypoglycemia type 5 (HHF5) [MIM:609968]. Familial hyperinsulinemic hypoglycemia [MIM:256450], also referred to as congenital hyperinsulinism, nesidioblastosis, or persistent hyperinsulinemic hypoglycemia of infancy (PPHI), is the most common cause of persistent hypoglycemia in infancy and is due to defective negative feedback regulation of insulin secretion by low glucose levels.[27] Defects in INSR are the cause of insulin-resistant diabetes mellitus with acanthosis nigricans type A (IRAN type A) [MIM:610549]. This syndrome is characterized by the association of severe insulin resistance (manifested by marked hyperinsulinemia and a failure to respond to exogenous insulin) with the skin lesion acanthosis nigricans and ovarian hyperandrogenism in adolescent female subjects. Women frequently present with hirsutism, acne, amenorrhea or oligomenorrhea, and virilization. This syndrome is different from the type B that has been demonstrated to be secondary to the presence of circulating autoantibodies against the insulin receptor. [INS_HUMAN] Defects in INS are the cause of familial hyperproinsulinemia (FHPRI) [MIM:176730].[28] [29] [30] [31] Defects in INS are a cause of diabetes mellitus insulin-dependent type 2 (IDDM2) [MIM:125852]. IDDM2 is a multifactorial disorder of glucose homeostasis that is characterized by susceptibility to ketoacidosis in the absence of insulin therapy. Clinical fetaures are polydipsia, polyphagia and polyuria which result from hyperglycemia-induced osmotic diuresis and secondary thirst. These derangements result in long-term complications that affect the eyes, kidneys, nerves, and blood vessels.[32] Defects in INS are a cause of diabetes mellitus permanent neonatal (PNDM) [MIM:606176]. PNDM is a rare form of diabetes distinct from childhood-onset autoimmune diabetes mellitus type 1. It is characterized by insulin-requiring hyperglycemia that is diagnosed within the first months of life. Permanent neonatal diabetes requires lifelong therapy.[33] [34] Defects in INS are a cause of maturity-onset diabetes of the young type 10 (MODY10) [MIM:613370]. MODY10 is a form of diabetes that is characterized by an autosomal dominant mode of inheritance, onset in childhood or early adulthood (usually before 25 years of age), a primary defect in insulin secretion and frequent insulin-independence at the beginning of the disease.[35] [36] [37]
Function
[INS_SHEEP] 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. [INSR_HUMAN] Receptor tyrosine kinase which mediates the pleiotropic actions of insulin. Binding of insulin leads to phosphorylation of several intracellular substrates, including, insulin receptor substrates (IRS1, 2, 3, 4), SHC, GAB1, CBL and other signaling intermediates. Each of these phosphorylated proteins serve as docking proteins for other signaling proteins that contain Src-homology-2 domains (SH2 domain) that specifically recognize different phosphotyrosines residues, including the p85 regulatory subunit of PI3K and SHP2. Phosphorylation of IRSs proteins lead to the activation of two main signaling pathways: the PI3K-AKT/PKB pathway, which is responsible for most of the metabolic actions of insulin, and the Ras-MAPK pathway, which regulates expression of some genes and cooperates with the PI3K pathway to control cell growth and differentiation. Binding of the SH2 domains of PI3K to phosphotyrosines on IRS1 leads to the activation of PI3K and the generation of phosphatidylinositol-(3, 4, 5)-triphosphate (PIP3), a lipid second messenger, which activates several PIP3-dependent serine/threonine kinases, such as PDPK1 and subsequently AKT/PKB. The net effect of this pathway is to produce a translocation of the glucose transporter SLC2A4/GLUT4 from cytoplasmic vesicles to the cell membrane to facilitate glucose transport. Moreover, upon insulin stimulation, activated AKT/PKB is responsible for: anti-apoptotic effect of insulin by inducing phosphorylation of BAD; regulates the expression of gluconeogenic and lipogenic enzymes by controlling the activity of the winged helix or forkhead (FOX) class of transcription factors. Another pathway regulated by PI3K-AKT/PKB activation is mTORC1 signaling pathway which regulates cell growth and metabolism and integrates signals from insulin. AKT mediates insulin-stimulated protein synthesis by phosphorylating TSC2 thereby activating mTORC1 pathway. The Ras/RAF/MAP2K/MAPK pathway is mainly involved in mediating cell growth, survival and cellular differentiation of insulin. Phosphorylated IRS1 recruits GRB2/SOS complex, which triggers the activation of the Ras/RAF/MAP2K/MAPK pathway. In addition to binding insulin, the insulin receptor can bind insulin-like growth factors (IGFI and IGFII). Isoform Short has a higher affinity for IGFII binding. When present in a hybrid receptor with IGF1R, binds IGF1. PubMed:12138094 shows that hybrid receptors composed of IGF1R and INSR isoform Long are activated with a high affinity by IGF1, with low affinity by IGF2 and not significantly activated by insulin, and that hybrid receptors composed of IGF1R and INSR isoform Short are activated by IGF1, IGF2 and insulin. In contrast, PubMed:16831875 shows that hybrid receptors composed of IGF1R and INSR isoform Long and hybrid receptors composed of IGF1R and INSR isoform Short have similar binding characteristics, both bind IGF1 and have a low affinity for insulin.[38] [39] [40] [41] [42] [43] [44] [45] [INS_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.
Publication Abstract from PubMed
The insulin receptor (IR) is a dimeric protein that plays a crucial role in controlling glucose homeostasis, regulating lipid, protein and carbohydrate metabolism, and modulating brain neurotransmitter levels(1,2). IR dysfunction has been associated with many diseases, including diabetes, cancer, and Alzheimer's disease(1,2,4). The primary sequence has been known since the 1980s(5), and is composed of an extracellular portion (ectodomain, ECD), a single transmembrane helix and an intracellular tyrosine kinase domain. Insulin binding to the dimeric ECD triggers kinase domain auto-phosphorylation and subsequent activation of downstream signaling molecules. Biochemical and mutagenesis data have identified two putative insulin binding sites (S1 and S2)(6). While insulin bound to an ECD fragment containing S1 and the apo ectodomain have been characterized structurally(7,8), details of insulin binding to the full receptor and the signal propagation mechanism are still not understood. Here we report single particle cryoEM reconstructions for the 1:2 (4.3 A) and 1:1 (7.4 A) IR ECD dimer:Insulin complexes. The symmetric 4.3 A structure shows two insulin molecules per dimer, each bound between the Leucine-rich sub domain L1 of one monomer and the first fibronectin-like domain (FnIII-1) of the other monomer, and making extensive interactions with the alpha subunit C-terminal helix (alpha-CT helix). The 7.4 A structure has only one similarly bound insulin per receptor dimer. The structures confirm the S1 binding interactions and define the full S2 binding site. These insulin receptor states suggest that recruitment of the alpha-CT helix upon binding of the first insulin changes the relative subdomain orientations and triggers downstream signal propagation.
Structure of the Insulin Receptor-Insulin Complex by Single Particle CryoEM analysis.,Scapin G, Dandey VP, Zhang Z, Prosise W, Hruza A, Kelly T, Mayhood T, Strickland C, Potter CS, Carragher B Nature. 2018 Feb 28. pii: nature26153. doi: 10.1038/nature26153. PMID:29512653[46]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Kadowaki T, Kadowaki H, Accili D, Taylor SI. Substitution of lysine for asparagine at position 15 in the alpha-subunit of the human insulin receptor. A mutation that impairs transport of receptors to the cell surface and decreases the affinity of insulin binding. J Biol Chem. 1990 Nov 5;265(31):19143-50. PMID:2121734
- ↑ Kadowaki T, Kadowaki H, Rechler MM, Serrano-Rios M, Roth J, Gorden P, Taylor SI. Five mutant alleles of the insulin receptor gene in patients with genetic forms of insulin resistance. J Clin Invest. 1990 Jul;86(1):254-64. PMID:2365819 doi:http://dx.doi.org/10.1172/JCI114693
- ↑ Krook A, Kumar S, Laing I, Boulton AJ, Wass JA, O'Rahilly S. Molecular scanning of the insulin receptor gene in syndromes of insulin resistance. Diabetes. 1994 Mar;43(3):357-68. PMID:8314008
- ↑ Longo N, Wang Y, Pasquali M. Progressive decline in insulin levels in Rabson-Mendenhall syndrome. J Clin Endocrinol Metab. 1999 Aug;84(8):2623-9. PMID:10443650
- ↑ Longo N, Wang Y, Smith SA, Langley SD, DiMeglio LA, Giannella-Neto D. Genotype-phenotype correlation in inherited severe insulin resistance. Hum Mol Genet. 2002 Jun 1;11(12):1465-75. PMID:12023989
- ↑ Tuthill A, Semple RK, Day R, Soos MA, Sweeney E, Seymour PJ, Didi M, O'rahilly S. Functional characterization of a novel insulin receptor mutation contributing to Rabson-Mendenhall syndrome. Clin Endocrinol (Oxf). 2007 Jan;66(1):21-6. PMID:17201797 doi:CEN2678
- ↑ Kadowaki T, Kadowaki H, Rechler MM, Serrano-Rios M, Roth J, Gorden P, Taylor SI. Five mutant alleles of the insulin receptor gene in patients with genetic forms of insulin resistance. J Clin Invest. 1990 Jul;86(1):254-64. PMID:2365819 doi:http://dx.doi.org/10.1172/JCI114693
- ↑ Longo N, Wang Y, Smith SA, Langley SD, DiMeglio LA, Giannella-Neto D. Genotype-phenotype correlation in inherited severe insulin resistance. Hum Mol Genet. 2002 Jun 1;11(12):1465-75. PMID:12023989
- ↑ Kadowaki T, Bevins CL, Cama A, Ojamaa K, Marcus-Samuels B, Kadowaki H, Beitz L, McKeon C, Taylor SI. Two mutant alleles of the insulin receptor gene in a patient with extreme insulin resistance. Science. 1988 May 6;240(4853):787-90. PMID:2834824
- ↑ Klinkhamer MP, Groen NA, van der Zon GC, Lindhout D, Sandkuyl LA, Krans HM, Moller W, Maassen JA. A leucine-to-proline mutation in the insulin receptor in a family with insulin resistance. EMBO J. 1989 Sep;8(9):2503-7. PMID:2479553
- ↑ Barbetti F, Gejman PV, Taylor SI, Raben N, Cama A, Bonora E, Pizzo P, Moghetti P, Muggeo M, Roth J. Detection of mutations in insulin receptor gene by denaturing gradient gel electrophoresis. Diabetes. 1992 Apr;41(4):408-15. PMID:1607067
- ↑ van der Vorm ER, van der Zon GC, Moller W, Krans HM, Lindhout D, Maassen JA. An Arg for Gly substitution at position 31 in the insulin receptor, linked to insulin resistance, inhibits receptor processing and transport. J Biol Chem. 1992 Jan 5;267(1):66-71. PMID:1730625
- ↑ al-Gazali LI, Khalil M, Devadas K. A syndrome of insulin resistance resembling leprechaunism in five sibs of consanguineous parents. J Med Genet. 1993 Jun;30(6):470-5. PMID:8326490
- ↑ Longo N, Langley SD, Griffin LD, Elsas LJ. Activation of glucose transport by a natural mutation in the human insulin receptor. Proc Natl Acad Sci U S A. 1993 Jan 1;90(1):60-4. PMID:8419945
- ↑ van der Vorm ER, Kuipers A, Kielkopf-Renner S, Krans HM, Moller W, Maassen JA. A mutation in the insulin receptor that impairs proreceptor processing but not insulin binding. J Biol Chem. 1994 May 13;269(19):14297-302. PMID:8188715
- ↑ Hone J, Accili D, al-Gazali LI, Lestringant G, Orban T, Taylor SI. Homozygosity for a new mutation (Ile119-->Met) in the insulin receptor gene in five sibs with familial insulin resistance. J Med Genet. 1994 Sep;31(9):715-6. PMID:7815442
- ↑ Longo N, Langley SD, Griffin LD, Elsas LJ. Two mutations in the insulin receptor gene of a patient with leprechaunism: application to prenatal diagnosis. J Clin Endocrinol Metab. 1995 May;80(5):1496-501. PMID:7538143
- ↑ Desbois-Mouthon C, Sert-Langeron C, Magre J, Oreal E, Blivet MJ, Flori E, Besmond C, Capeau J, Caron M. Deletion of Asn281 in the alpha-subunit of the human insulin receptor causes constitutive activation of the receptor and insulin desensitization. J Clin Endocrinol Metab. 1996 Feb;81(2):719-27. PMID:8636294
- ↑ Kadowaki H, Takahashi Y, Ando A, Momomura K, Kaburagi Y, Quin JD, MacCuish AC, Koda N, Fukushima Y, Taylor SI, Akanuma Y, Yazaki Y, Kadowaki T. Four mutant alleles of the insulin receptor gene associated with genetic syndromes of extreme insulin resistance. Biochem Biophys Res Commun. 1997 Aug 28;237(3):516-20. PMID:9299395 doi:S0006-291X(97)97181-3
- ↑ Desbois-Mouthon C, Girodon E, Ghanem N, Caron M, Pennerath A, Conteville P, Magre J, Besmond C, Goossens M, Capeau J, Amselem S. Molecular analysis of the insulin receptor gene for prenatal diagnosis of leprechaunism in two families. Prenat Diagn. 1997 Jul;17(7):657-63. PMID:9249867
- ↑ Whitehead JP, Soos MA, Jackson R, Tasic V, Kocova M, O'Rahilly S. Multiple molecular mechanisms of insulin receptor dysfunction in a patient with Donohue syndrome. Diabetes. 1998 Aug;47(8):1362-4. PMID:9703342
- ↑ George S, Johansen A, Soos MA, Mortensen H, Gammeltoft S, Saudek V, Siddle K, Hansen L, O'Rahilly S. Deletion of V335 from the L2 domain of the insulin receptor results in a conformationally abnormal receptor that is unable to bind insulin and causes Donohue's syndrome in a human subject. Endocrinology. 2003 Feb;144(2):631-7. PMID:12538626
- ↑ Maassen JA, Tobias ES, Kayserilli H, Tukel T, Yuksel-Apak M, D'Haens E, Kleijer WJ, Fery F, van der Zon GC. Identification and functional assessment of novel and known insulin receptor mutations in five patients with syndromes of severe insulin resistance. J Clin Endocrinol Metab. 2003 Sep;88(9):4251-7. PMID:12970295
- ↑ Cocozza S, Porcellini A, Riccardi G, Monticelli A, Condorelli G, Ferrara A, Pianese L, Miele C, Capaldo B, Beguinot F, et al.. NIDDM associated with mutation in tyrosine kinase domain of insulin receptor gene. Diabetes. 1992 Apr;41(4):521-6. PMID:1607076
- ↑ Kasuga M, Kishimoto M, Hashiramoto M, Yonezawa K, Kazumi T, Hagino H, Shii K. [Insulin receptor Arg1131-->Gln: a novel mutation in the catalytic loop of insulin receptor observed in insulin resistant diabetes] Nippon Geka Gakkai Zasshi. 1992 Sep;93(9):968-71. PMID:1470163
- ↑ Kan M, Kanai F, Iida M, Jinnouchi H, Todaka M, Imanaka T, Ito K, Nishioka Y, Ohnishi T, Kamohara S, et al.. Frequency of mutations of insulin receptor gene in Japanese patients with NIDDM. Diabetes. 1995 Sep;44(9):1081-6. PMID:7657032
- ↑ Hojlund K, Hansen T, Lajer M, Henriksen JE, Levin K, Lindholm J, Pedersen O, Beck-Nielsen H. A novel syndrome of autosomal-dominant hyperinsulinemic hypoglycemia linked to a mutation in the human insulin receptor gene. Diabetes. 2004 Jun;53(6):1592-8. PMID:15161766
- ↑ Chan SJ, Seino S, Gruppuso PA, Schwartz R, Steiner DF. A mutation in the B chain coding region is associated with impaired proinsulin conversion in a family with hyperproinsulinemia. Proc Natl Acad Sci U S A. 1987 Apr;84(8):2194-7. PMID:3470784
- ↑ Barbetti F, Raben N, Kadowaki T, Cama A, Accili D, Gabbay KH, Merenich JA, Taylor SI, Roth J. Two unrelated patients with familial hyperproinsulinemia due to a mutation substituting histidine for arginine at position 65 in the proinsulin molecule: identification of the mutation by direct sequencing of genomic deoxyribonucleic acid amplified by polymerase chain reaction. J Clin Endocrinol Metab. 1990 Jul;71(1):164-9. PMID:2196279
- ↑ Shibasaki Y, Kawakami T, Kanazawa Y, Akanuma Y, Takaku F. Posttranslational cleavage of proinsulin is blocked by a point mutation in familial hyperproinsulinemia. J Clin Invest. 1985 Jul;76(1):378-80. PMID:4019786 doi:http://dx.doi.org/10.1172/JCI111973
- ↑ Yano H, Kitano N, Morimoto M, Polonsky KS, Imura H, Seino Y. A novel point mutation in the human insulin gene giving rise to hyperproinsulinemia (proinsulin Kyoto). J Clin Invest. 1992 Jun;89(6):1902-7. PMID:1601997 doi:http://dx.doi.org/10.1172/JCI115795
- ↑ Molven A, Ringdal M, Nordbo AM, Raeder H, Stoy J, Lipkind GM, Steiner DF, Philipson LH, Bergmann I, Aarskog D, Undlien DE, Joner G, Sovik O, Bell GI, Njolstad PR. Mutations in the insulin gene can cause MODY and autoantibody-negative type 1 diabetes. Diabetes. 2008 Apr;57(4):1131-5. doi: 10.2337/db07-1467. Epub 2008 Jan 11. PMID:18192540 doi:10.2337/db07-1467
- ↑ Stoy J, Edghill EL, Flanagan SE, Ye H, Paz VP, Pluzhnikov A, Below JE, Hayes MG, Cox NJ, Lipkind GM, Lipton RB, Greeley SA, Patch AM, Ellard S, Steiner DF, Hattersley AT, Philipson LH, Bell GI. Insulin gene mutations as a cause of permanent neonatal diabetes. Proc Natl Acad Sci U S A. 2007 Sep 18;104(38):15040-4. Epub 2007 Sep 12. PMID:17855560 doi:10.1073/pnas.0707291104
- ↑ Edghill EL, Flanagan SE, Patch AM, Boustred C, Parrish A, Shields B, Shepherd MH, Hussain K, Kapoor RR, Malecki M, MacDonald MJ, Stoy J, Steiner DF, Philipson LH, Bell GI, Hattersley AT, Ellard S. Insulin mutation screening in 1,044 patients with diabetes: mutations in the INS gene are a common cause of neonatal diabetes but a rare cause of diabetes diagnosed in childhood or adulthood. Diabetes. 2008 Apr;57(4):1034-42. Epub 2007 Dec 27. PMID:18162506 doi:10.2337/db07-1405
- ↑ Molven A, Ringdal M, Nordbo AM, Raeder H, Stoy J, Lipkind GM, Steiner DF, Philipson LH, Bergmann I, Aarskog D, Undlien DE, Joner G, Sovik O, Bell GI, Njolstad PR. Mutations in the insulin gene can cause MODY and autoantibody-negative type 1 diabetes. Diabetes. 2008 Apr;57(4):1131-5. doi: 10.2337/db07-1467. Epub 2008 Jan 11. PMID:18192540 doi:10.2337/db07-1467
- ↑ Edghill EL, Flanagan SE, Patch AM, Boustred C, Parrish A, Shields B, Shepherd MH, Hussain K, Kapoor RR, Malecki M, MacDonald MJ, Stoy J, Steiner DF, Philipson LH, Bell GI, Hattersley AT, Ellard S. Insulin mutation screening in 1,044 patients with diabetes: mutations in the INS gene are a common cause of neonatal diabetes but a rare cause of diabetes diagnosed in childhood or adulthood. Diabetes. 2008 Apr;57(4):1034-42. Epub 2007 Dec 27. PMID:18162506 doi:10.2337/db07-1405
- ↑ Boesgaard TW, Pruhova S, Andersson EA, Cinek O, Obermannova B, Lauenborg J, Damm P, Bergholdt R, Pociot F, Pisinger C, Barbetti F, Lebl J, Pedersen O, Hansen T. Further evidence that mutations in INS can be a rare cause of Maturity-Onset Diabetes of the Young (MODY). BMC Med Genet. 2010 Mar 12;11:42. doi: 10.1186/1471-2350-11-42. PMID:20226046 doi:10.1186/1471-2350-11-42
- ↑ Kasuya J, Paz IB, Maddux BA, Goldfine ID, Hefta SA, Fujita-Yamaguchi Y. Characterization of human placental insulin-like growth factor-I/insulin hybrid receptors by protein microsequencing and purification. Biochemistry. 1993 Dec 14;32(49):13531-6. PMID:8257688
- ↑ Soos MA, Field CE, Siddle K. Purified hybrid insulin/insulin-like growth factor-I receptors bind insulin-like growth factor-I, but not insulin, with high affinity. Biochem J. 1993 Mar 1;290 ( Pt 2):419-26. PMID:8452530
- ↑ Van Horn DJ, Myers MG Jr, Backer JM. Direct activation of the phosphatidylinositol 3'-kinase by the insulin receptor. J Biol Chem. 1994 Jan 7;269(1):29-32. PMID:8276809
- ↑ Sawka-Verhelle D, Filloux C, Tartare-Deckert S, Mothe I, Van Obberghen E. Identification of Stat 5B as a substrate of the insulin receptor. Eur J Biochem. 1997 Dec 1;250(2):411-7. PMID:9428692
- ↑ Frasca F, Pandini G, Scalia P, Sciacca L, Mineo R, Costantino A, Goldfine ID, Belfiore A, Vigneri R. Insulin receptor isoform A, a newly recognized, high-affinity insulin-like growth factor II receptor in fetal and cancer cells. Mol Cell Biol. 1999 May;19(5):3278-88. PMID:10207053
- ↑ Pandini G, Frasca F, Mineo R, Sciacca L, Vigneri R, Belfiore A. Insulin/insulin-like growth factor I hybrid receptors have different biological characteristics depending on the insulin receptor isoform involved. J Biol Chem. 2002 Oct 18;277(42):39684-95. Epub 2002 Jul 22. PMID:12138094 doi:10.1074/jbc.M202766200
- ↑ Fiory F, Alberobello AT, Miele C, Oriente F, Esposito I, Corbo V, Ruvo M, Tizzano B, Rasmussen TE, Gammeltoft S, Formisano P, Beguinot F. Tyrosine phosphorylation of phosphoinositide-dependent kinase 1 by the insulin receptor is necessary for insulin metabolic signaling. Mol Cell Biol. 2005 Dec;25(24):10803-14. PMID:16314505 doi:10.1128/MCB.25.24.10803-10814.2005
- ↑ Slaaby R, Schaffer L, Lautrup-Larsen I, Andersen AS, Shaw AC, Mathiasen IS, Brandt J. Hybrid receptors formed by insulin receptor (IR) and insulin-like growth factor I receptor (IGF-IR) have low insulin and high IGF-1 affinity irrespective of the IR splice variant. J Biol Chem. 2006 Sep 8;281(36):25869-74. Epub 2006 Jul 10. PMID:16831875 doi:10.1074/jbc.M605189200
- ↑ 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
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