Editing Insulin receptor (section)

== Structure ==
Initially, [[transcription (genetics)|transcription]] of alternative splice variants derived from the ''INSR'' gene are [[translation (genetics)|translated]] to form one of two monomeric isomers; IR-A in which [[exon]] 11 is excluded, and IR-B in which exon 11 is included. Inclusion of exon 11 results in the addition of 12 amino acids upstream of the intrinsic [[furin]] proteolytic cleavage site. [[Image:Colour coded Schematic of the Insulin Receptor.png|left|thumbnail|350px|Colour-coded schematic of the insulin receptor]]

Upon receptor dimerisation, after [[Proteolysis|proteolytic cleavage]] into the α- and β-chains, the additional 12 amino acids remain present at the [[C-terminus]] of the α-chain (designated αCT) where they are predicted to influence receptor–[[ligand]] interaction.<ref name="pmid21838706">{{cite journal | vauthors = Knudsen L, De Meyts P, Kiselyov VV | title = Insight into the molecular basis for the kinetic differences between the two insulin receptor isoforms | journal = The Biochemical Journal | volume = 440 | issue = 3 | pages = 397–403 | date = December 2011 | pmid = 21838706 | doi = 10.1042/BJ20110550 | url = https://hal.archives-ouvertes.fr/hal-00658157/file/PEER_stage2_10.1042%252FBJ20110550.pdf }}</ref>

Each isometric [[monomer]] is structurally organized into 8 distinct domains consists of; a leucine-rich repeat domain (L1, residues 1–157), a cysteine-rich region (CR, residues 158–310), an additional leucine rich repeat domain (L2, residues 311–470), three [[fibronectin type III domain]]s; FnIII-1 (residues 471–595), FnIII-2 (residues 596–808) and FnIII-3 (residues 809–906). Additionally, an insert domain (ID, residues 638–756) resides within FnIII-2, containing the α/β furin cleavage site, from which proteolysis results in both IDα and IDβ domains. Within the β-chain, downstream of the FnIII-3 domain lies a transmembrane helix (TH) and intracellular juxtamembrane (JM) region, just upstream of the intracellular tyrosine kinase (TK) catalytic domain, responsible for subsequent intracellular signaling pathways.<ref name="pmid20348418">{{cite journal | vauthors = Smith BJ, Huang K, Kong G, Chan SJ, Nakagawa S, Menting JG, Hu SQ, Whittaker J, Steiner DF, Katsoyannis PG, Ward CW, Weiss MA, Lawrence MC | title = Structural resolution of a tandem hormone-binding element in the insulin receptor and its implications for design of peptide agonists | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 107 | issue = 15 | pages = 6771–6 | date = April 2010 | pmid = 20348418 | pmc = 2872410 | doi = 10.1073/pnas.1001813107 | bibcode = 2010PNAS..107.6771S | doi-access = free }}</ref>

Upon cleavage of the monomer to its respective α- and β-chains, receptor hetero or homo-dimerisation is maintained covalently between chains by a single disulphide link and between monomers in the dimer by two disulphide links extending from each α-chain. The overall 3D [[ectodomain]] structure, possessing four ligand binding sites, resembles an inverted 'V', with the each monomer rotated approximately 2-fold about an axis running parallel to the inverted 'V' and L2 and FnIII-1 domains from each monomer forming the inverted 'V's apex.<ref name="pmid20348418"/><ref name="pmid16957736">{{cite journal | vauthors = McKern NM, Lawrence MC, Streltsov VA, Lou MZ, Adams TE, Lovrecz GO, Elleman TC, Richards KM, Bentley JD, Pilling PA, Hoyne PA, Cartledge KA, Pham TM, Lewis JL, Sankovich SE, Stoichevska V, Da Silva E, Robinson CP, Frenkel MJ, Sparrow LG, Fernley RT, Epa VC, Ward CW | title = Structure of the insulin receptor ectodomain reveals a folded-over conformation | journal = Nature | volume = 443 | issue = 7108 | pages = 218–21 | date = September 2006 | pmid = 16957736 | doi = 10.1038/nature05106 | bibcode = 2006Natur.443..218M | s2cid = 4381431 }}</ref>