The Structure of Interleukin-2 Complexed with Its Alpha Receptor

Abstract

Interleukin-2 (IL-2) is an immunoregulatory cytokine that binds sequentially to the alpha (IL-2Rα), beta (IL-2Rβ), and common gamma chain (γ c ) receptor subunits. Here we present the 2.8 angstrom crystal structure of a complex between human IL-2 and IL-2Rα, which interact in a docking mode distinct from that of other cytokine receptor complexes. IL-2Rα is composed of strand-swapped “sushi-like” domains, unlike the classical cytokine receptor fold. As a result of this domain swap, IL-2Rα 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.