Localization and synthesis of an insulin-binding region on human insulin receptor

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Abstract
Seven regions of the α subunit of human insulin receptor (HIR) were synthesized and examined for their ability to bind radioiodinated insulin. A peptide representing one of these regions (namely, residues α655–670) exhibited a specific binding activity for insulin. In quantitative radiometric titrations, the binding curves of125I-labeled insulin to adsorbents of peptide α655–670 and of purified placental membrane were similar or superimposable. The binding of radioiodinated insulin to peptide or to membrane adsorbents was completely inhibited by unlabeled insulin, and the inhibition curves indicated that the peptide and the membrane on the adsorbents had similar affinities. Synthetic peptides that were shorter (peptide α661–670) or longer (peptide α651–670) than the region α655–670 exhibited lower insulin-binding activity. It was concluded that an insulin-binding region in the HIR α subunit resides within residues α655–670. The results do not rule out the possibility that other regions of the α subunit may also participate in binding of HIR to insulin, with the region described here forming a “face” within a larger binding site.