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-2Ralpha), beta (IL-2Rbeta), and common gamma chain (gammac) receptor subunits. Here we present the 2.8 angstrom crystal structure of a complex between human IL-2 and IL-2Ralpha, which interact in a docking mode distinct from that of other cytokine receptor complexes. IL-2Ralpha is composed of strand-swapped "sushi-like" domains, unlike the classical cytokine receptor fold. As a result of this domain swap, IL-2Ralpha 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.
Rickert
Mathias
M
Departments of Microbiology and Immunology, and Structural Biology, Stanford University School of Medicine, 299 Campus Drive, Fairchild D319, Stanford, CA 94305-5124, USA.
Wang
Xinquan
X
Boulanger
Martin J
MJ
Goriatcheva
Natalia
N
Garcia
K Christopher
KC
D018360:Crystallography, X-Ray; D006801:Humans; D007376:Interleukin-2 / Q000737:chemistry* / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D018123:Receptors, Interleukin / Q000737:chemistry* / Q000378:metabolism
C508017:IL2RA protein, human; D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit; D018123:Receptors, Interleukin