Solution Assembly of a Soluble, Heteromeric, High Affinity Interleukin-2 Receptor Complex

Abstract

In this study, we report the use of coiled-coil (leucine zipper) molecular recognition for the solution assembly of stable, high affinity, heteromeric interleukin-2 receptor complexes. Co-expression of interleukin-2 receptor α and β extracellular domains (ectodomains), each fused to seven coiled-coil heptad repeats, resulted in the formation of heteromeric complexes that bound interleukin-2 in a cooperative fashion and with much higher affinity than similar homomeric complexes. The dissociation constants for these solution complexes are within the range of values reported for the comparable cell surface “pseudo high affinity” interleukin-2 receptor. Ligand-induced cross-linking of homomeric or heteromeric receptor subunits is the common signal transmission mechanism employed by hematopoietin receptors. Individual receptor ectodomains, however, often do not bind ligand with measurable affinity. This is the first study to demonstrate the feasibility of coiled-coil mediated preassembly of cytokine receptor complexes.

Department

Molecular, Cellular and Biomedical Sciences

Publication Date

7-7-1995

Journal Title

The Journal of Biological Chemistry

Publisher

American Society for Biochemistry and Molecular Biology

Document Type

Article

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