Structure
Initially, transcription of alternative splice variants derived from the INSR gene are translated to form one of two monomeric isomers; IR-A in which exon 11 is omitted, and IR-B in which exon 11 is included. Inclusion of exon 11 results in the addition of 12 amino acids upstream of the inherit furin protyolytic cleavage site.
Upon receptor dimerisation, after protyolytic 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.
Each isometric monomer is structurally organized into 8 distinct domains consists of; a leucine-rich repeat domain (L1, residues 1-157), a cyctine rich region (CR, residues 158-310), an additional leucine rich repeat domain (L2, residues 311-470), three fibronectin type III domains; 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.
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.
Read more about this topic: Insulin Receptor
Famous quotes containing the word structure:
“A special feature of the structure of our book is the monstrous but perfectly organic part that eavesdropping plays in it.”
—Vladimir Nabokov (1899–1977)
“Agnosticism is a perfectly respectable and tenable philosophical position; it is not dogmatic and makes no pronouncements about the ultimate truths of the universe. It remains open to evidence and persuasion; lacking faith, it nevertheless does not deride faith. Atheism, on the other hand, is as unyielding and dogmatic about religious belief as true believers are about heathens. It tries to use reason to demolish a structure that is not built upon reason.”
—Sydney J. Harris (1917–1986)
“Women over fifty already form one of the largest groups in the population structure of the western world. As long as they like themselves, they will not be an oppressed minority. In order to like themselves they must reject trivialization by others of who and what they are. A grown woman should not have to masquerade as a girl in order to remain in the land of the living.”
—Germaine Greer (b. 1939)