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

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

Source

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; [PubMed - indexed for MEDLINE]

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PDB/2B5I

Grant Support

AI51321/AI/NIAID NIH HHS/United States

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Structures reported by this article

Cytokine Receptor Complex

PDB: 2B5I

Source: Homo sapiens

Method: X-Ray Diffraction

Resolution: 2.3 Å

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