Structure of the Quaternary Complex of Interleukin-2 with Its α, β, and γc Receptors
Abstract
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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We thank N. Goriatcheva for expert technical assistance; K. Smith, T. Springer, and W. Leonard for helpful discussions; and the Advanced Light Source (UC-Berkeley) and Stanford Synchrotron Radiation Laboratory for synchrotron beamtime. Supported by the Keck Foundation, HHMI, and NIH grant AI51321. Coordinates and structure factors have been deposited in the Protein Data Bank with accession number 2B5I.
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Published In
Science
Volume 310 | Issue 5751
18 November 2005
18 November 2005
Copyright
American Association for the Advancement of Science.
Submission history
Received: 25 July 2005
Accepted: 14 October 2005
Published in print: 18 November 2005
Notes
Supporting Online Material
www.sciencemag.org/cgi/content/full/310/5751/1159/DC1
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Figs. S1 to S3
Tables S1 and S2
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