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