Coiled-coil molecular recognition: directed solution assembly of receptor ectodomains

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Abstract
The high affinity interleukin-2 (IL-2) receptor is composed of at least three cell surface proteins (α, β and γ subunits), each of which is independently capable of ligand binding. Physiologically, these subunits cooperate to form dimeric and trimeric complexes that efficiently capture IL-2 and transmit the signal across the membrane. The knowledge of how each subunit functions with respect to ligand capture, signal transmission and internalization is essential for the development of ligand-based IL-2 agonists and antagonists, as well as receptor-related therapeutic and diagnostic reagents. Only one of the subunits (p55 or α chain) is capable of interacting with ligand in solution in a manner that resembles cell surface binding. To generate soluble multhnerk complexes of the IL-2 receptor subunits that may bind ligand in solution in a fashion that mimics the same receptor complexes on the cell surface, we have added recognition sequences (coiled-coil heptad repeats) to the ectodomains of the individual receptors. Here we describe the expression and characterization of a prototype IL-2β receptor ectodomain-coiled-coil fusion protein and demonstrate that this is a feasible approach to the preparation of cytokine receptor solution complexes.

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