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Science 308 (5727): 1477-1480

Copyright © 2005 by the American Association for the Advancement of Science

The Structure of Interleukin-2 Complexed with Its Alpha Receptor

Mathias Rickert,* Xinquan Wang,* Martin J. Boulanger, Natalia Goriatcheva, K. Christopher Garcia{dagger}

Abstract: Interleukin-2 (IL-2) is an immunoregulatory cytokine that binds sequentially to the alpha (IL-2R{alpha}), beta (IL-2Rß), 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.

Departments of Microbiology and Immunology, and Structural Biology, Stanford University School of Medicine, 299 Campus Drive, Fairchild D319, Stanford, CA 94305–5124, USA.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: kcgarcia{at}

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