Interactions of a hybrid insulin/insulin-like growth factor-I analog with chimeric insulin/type I insulin-like growth factor receptors

L. Schaffer, T. Kjeldsen, A. S. Andersen, F. C. Wiberg, U. D. Larsen, J. F. Cara, R. G. Mirmira, S. H. Nakagawa, H. S. Tager

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

We have examined, by use of a hybrid insulin/insulin-like growth factor-I analog and chimeric insulin/type I insulin-like growth factor receptors, the interplay between ligand and receptor structure in determining the affinity and specificity of hormone-receptor interactions in the insulin and insulin- like growth factor-I systems. Our findings, obtained through the study of radiolabeled peptide binding to detergent-solubilized full-length receptors and to soluble truncated receptors, show that (a) the two-chain hybrid analog exhibits significant cross-reactivity with both receptor systems, (b) the exchange of appropriate domains in chimeric receptors enhances the receptor binding affinity of the analog by 3.5-21-fold, and (c) the affinity of the hybrid analog for the chimeric receptors actually exceeds that of either natural insulin or natural insulin-like growth factor-I. We conclude that the specificity-conferring domains of the insulin and type I insulin-like growth factor receptors reside in different regions of a common binding site, and that the exchange of domains between pairs of related hormones and between pairs of related receptors can yield new ligand-receptor systems with significantly altered affinities and selectivities.

Original languageEnglish (US)
Pages (from-to)3044-3047
Number of pages4
JournalJournal of Biological Chemistry
Volume268
Issue number5
StatePublished - Jan 1 1993
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Schaffer, L., Kjeldsen, T., Andersen, A. S., Wiberg, F. C., Larsen, U. D., Cara, J. F., Mirmira, R. G., Nakagawa, S. H., & Tager, H. S. (1993). Interactions of a hybrid insulin/insulin-like growth factor-I analog with chimeric insulin/type I insulin-like growth factor receptors. Journal of Biological Chemistry, 268(5), 3044-3047.