Insulin-like growth factor: a model for tertiary structure accounting for immunoreactivity and receptor binding.
A model for the three-dimensional structure of insulin-like growth factor (IGF) is proposed based on the close sequence homology of IGF with insulin, the tertiary structure of which is known. The IGF molecule is postulated to have an insulin-like main chain conformation for residues equivalent to B6--B27 and A1--A21 and a hydrophobic core nearly identical to that of insulin. A short connecting peptide of twelve residues and an extension at the COOH-terminus are easily accommodated on the molecular surface. The surface involved in dimer formation in insulin is largely conserved, but the zinc-binding histidine and many residues involving hexamerization are very different from those of insulin and it is unlikely that IGF forms zinc hexamers. The model provides a ready explanation for the inability of IGF to bind antibodies to insulin and for its ability to bind insulin receptors with low affinity.
D000595:Amino Acid Sequence; D003429:Cross Reactions; D006133:Growth Substances / Q000276:immunology / Q000378:metabolism; D007328:Insulin / Q000276:immunology / Q000378:metabolism; D011487:Protein Conformation; D011972:Receptor, Insulin / Q000378:metabolism; D013002:Somatomedins / Q000276:immunology / Q000378:metabolism
D006133:Growth Substances; D007328:Insulin; D011972:Receptor, Insulin; D013002:Somatomedins
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