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Science. 2005 Nov 18;310(5751):1159-63.

Structure of the quaternary complex of interleukin-2 with its alpha, beta, and gammac receptors.

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1
Howard Hughes Medical Institute, Department of Microbiology and Immunology, Stanford University School of Medicine, 299 Campus Drive, Fairchild D319, Stanford, CA 94305, USA.

Abstract

Interleukin-2 (IL-2) is an immunoregulatory cytokine that acts through a quaternary receptor signaling complex containing alpha (IL-2Ralpha), beta (IL-2Rbeta), 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-2Ralpha to IL-2 stabilizes a secondary binding site for presentation to IL-2Rbeta. gammac is then recruited to the composite surface formed by the IL-2/IL-2Rbeta complex. Consistent with its role as a shared receptor for IL-4, IL-7, IL-9, IL-15, and IL-21, gammac forms degenerate contacts with IL-2. The structure of gammac 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 gammac-dependent cytokine-receptor interactions and for the engineering of improved IL-2 therapeutics.

PMID:
16293754
DOI:
10.1126/science.1117893
[Indexed for MEDLINE]
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