Research Article

Structure of the Quaternary Complex of Interleukin-2 with Its α, ß, and γc Receptors

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Science  18 Nov 2005:
Vol. 310, Issue 5751, pp. 1159-1163
DOI: 10.1126/science.1117893

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Interleukin-2 (IL-2) is an immunoregulatory cytokine that acts through a quaternary receptor signaling complex containing alpha (IL-2Rα), beta (IL-2Rβ), and common gamma chain (gc) receptors. In the structure of the quaternary ectodomain complex as visualized at a resolution of 2.3 angstroms, the binding of IL-2Rα to IL-2 stabilizes a secondary binding site for presentation to IL-2Rβ. γc is then recruited to the composite surface formed by the IL-2/IL-2Rβ complex. Consistent with its role as a shared receptor for IL-4, IL-7, IL-9, IL-15, and IL-21, γc forms degenerate contacts with IL-2. The structure of γc provides a rationale for loss-of-function mutations found in patients with X-linked severe combined immunodeficiency diseases (X-SCID). This complex structure provides a framework for other γc-dependent cytokine-receptor interactions and for the engineering of improved IL-2 therapeutics.

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