The structure of interleukin-2 complexed with its alpha receptor

Interleukin-2 (IL-2) is an immunoregulatory cytokine that binds sequentially to the alpha (IL-2R alpha), beta (IL-2R beta), and common gamma chain (gamma(c)) receptor subunits. Here we present the 2.8 angstrom crystal structure of a complex between human IL-2 and IL-2R alpha, which-interact in a docking mode distinct from that of other cytokine receptor complexes. IL-2R alpha is composed of strand-swapped sushi-like domains, unlike the classical cytokine receptor fold. As a result of this domain swap, IL-2R alpha uses a composite surface to dock into a groove on IL-2 that also serves as a binding site for antagonist drugs. With this complex, we now have representative structures for each class of hematopoietic cytokine receptor-docking modules.