The binding sites of insulin-like growth factor I (IGF I) to type I IGF receptor and to a monoclonal antibody. Mapping by chemical modification of tyrosine residues

J Biol Chem. 1988 May 25;263(15):7068-72.

Abstract

The surface topography of IGF I(insulin-like growth factor I) was investigated by chemical modification of amino acid residues in free IGF I and bound to type I IGF receptor or to monoclonal antibody MAB43. Tyrosine residues were modified either by chloramine-T or lactoperoxidase catalyzed iodination. In the free IGF I molecule, all 3 tyrosine residues, A19 (Tyr-60), B25 (Tyr-24), and C2 (Tyr-31), were iodinated. Monoclonal antibody MAB43 protected IGF I against modification at tyrosine residue A19, and in the type I IGF receptor-IGF I complex, all 3 tyrosine residues were shielded against iodine incorporation. These results allow the prediction of the binding domains in the IGF I molecule. The minimal receptor binding site in IGF I would include amino acid residues B25 to C2 and, possibly, the C-terminal part of the A-domain with tyrosine residue A19.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Antibodies, Monoclonal
  • Antigen-Antibody Complex
  • Female
  • Humans
  • Insulin-Like Growth Factor I / immunology
  • Insulin-Like Growth Factor I / metabolism*
  • Models, Molecular
  • Molecular Sequence Data
  • Molecular Weight
  • Peptide Fragments / analysis
  • Placenta / metabolism
  • Pregnancy
  • Protein Conformation
  • Receptor, Insulin / metabolism*
  • Receptors, Somatomedin
  • Somatomedins / metabolism*
  • Trypsin

Substances

  • Antibodies, Monoclonal
  • Antigen-Antibody Complex
  • Peptide Fragments
  • Receptors, Somatomedin
  • Somatomedins
  • Insulin-Like Growth Factor I
  • Receptor, Insulin
  • Trypsin