Structural View of Cytokine Interactions

Science's STKE  22 Nov 2005:
Vol. 2005, Issue 311, pp. tw417
DOI: 10.1126/stke.3112005tw417

Interleukin-2 (IL-2), a cytokine produced by activated T cells, promotes the proliferation, differentiation, and survival of mature T and B cells. Its actions are primarily mediated through a quaternary signaling complex that consists of IL-2, the α and β receptors (IL-2Rα, IL-2Rβ), and the γc chain. Now Wang et al. present the extracellular structure of the quaternary complex at 2.3 angstroms resolution. Besides providing insight into IL-2 interactions that might facilitate design of IL-2 agonists and inhibitors, the structure provides a view of the γc receptor. This receptor is shared for IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21 and is mutated in X-linked severe combined immunodeficiency diseases (X-SCID). Several mutations associated with X-SCID map to residues in the γc binding sites.

X. Wang, M. Rickert, K. C. Garcia, Structure of the quaternary complex of interleukin–2 with its α, β, and γc receptors. Science 310, 1159–1163 (2005). [Abstract] [Full Text]