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Structural domains of the insulin receptor and IGF receptor required for dimerisation and ligand binding
Author(s) -
Molina L,
Marino-Buslje C,
Quinn D.R,
Siddle K
Publication year - 2000
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(00)01161-3
Subject(s) - receptor , monomer , chemistry , protein subunit , ligand (biochemistry) , insulin receptor , peptide , biochemistry , amino acid , c terminus , insulin , stereochemistry , biology , endocrinology , gene , insulin resistance , organic chemistry , polymer
We investigated structural requirements for dimerisation and ligand binding of insulin/IGF receptors. Soluble receptor fragments consisting of N‐terminal domains (L1/CYS/L2, L1/CYS/L2/F0) or fibronectin domains (F0/F1/F2, F1/F2) were expressed in CHO cells. Fragments containing F0 or F1 domains were secreted as disulphide‐linked dimers, and those consisting of L1/CYS/L2 domains as monomers. None of these proteins bound ligand. However, when a peptide of 16 amino acids from the α‐subunit C‐terminus was fused to the C‐terminus of L1/CYS/L2, the monomeric insulin and IGF receptor constructs bound their respective ligands with affinity only 10‐fold lower than native receptors.