Cytokine receptor activation at the cell surface

Cytokines are well recognized for the pleiotropic nature of their signaling and biological activities on many cell types and their role in health and disease. Recent years have seen a steady stream of new cytokine receptor crystal structures including those that are activated by GM-CSF, type I interferon, and a variety of interleukins. Highlights include the observation of a dodecameric signaling complex for the GM-CSF receptor, electron microscopy imaging of an intact gp130/IL-6/IL-6Rα ternary receptor complex bound to its signal transducing Janus kinase and visualization of novel cytokine recognition mechanisms in the interleukin-17 and type I interferon families. This increasing knowledge in cytokine structural biology is driving new opportunities for developing novel therapies to modulate cytokine function in a diverse range of diseases including malignancies and chronic inflammation.

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► Structure of the GM-CSF receptor complex reveals a dodecameric signaling unit.
► N-glycosylation of IL-7 receptor found critical for high affinity binding of IL-7.
► Structure of an IL-17R complex reveals a novel mode of cytokine recognition.
► Type 1 interferon receptors recognize diverse cytokines through ‘anchor points’.
► Visualization of intact gp130/IL-6/IL-6Rα ternary receptor bound to a Janus kinase.