SOLUTION ASSEMBLY OF A SOLUBLE, HETEROMERIC, HIGH-AFFINITY INTERLEUKIN-2 RECEPTOR COMPLEX

In this study, we report the use of coiled-coil (leucine zipper) molec ular recognition for the solution assembly of stable, high affinity, h eteromeric interleukin-2 receptor complexes, Co-expression of interleu kin-2 receptor alpha and beta extracellular domains (ectodomains), eac h fused to seven coiled-coil heptad repeats, resulted in the formation of heteromeric complexes that bound interleukin-2 in a cooperative fa shion 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 hig h affinity'' interleukin-2 receptor. Ligand-induced cross-linking of h omomeric or heteromeric receptor subunits is the common signal transmi ssion mechanism employed by hematopoietin receptors. Individual recept or ectodomains, however, often do not bind ligand with measurable affi nity, This is the first study to demonstrate the feasibility of coiled coil mediated preassembly of cytokine receptor complexes.