Structural domains of the insulin receptor and IGF receptor required for dimerisation and ligand binding.
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 alpha-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.
Molina
L
L
Department of Clinical Biochemistry, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK.
Marino-Buslje
C
C
Quinn
D R
DR
Siddle
K
K
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D016466:CHO Cells; D006224:Cricetinae; D018076:DNA, Complementary / Q000096:biosynthesis; D019281:Dimerization; D008024:Ligands; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000096:biosynthesis / Q000235:genetics; D011972:Receptor, Insulin / Q000737:chemistry* / Q000235:genetics; D017451:Receptors, Somatomedin / Q000737:chemistry* / Q000235:genetics
D018076:DNA, Complementary; D008024:Ligands; D010446:Peptide Fragments; D017451:Receptors, Somatomedin; D011972:Receptor, Insulin