Structure of the activating IL-1 receptor signaling complex

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Abstract

Interleukin-1 (IL-1)-family cytokines are mediators of innate and adaptive immunity. They exert proinflammatory effects by binding a primary receptor that recruits a receptor accessory protein to form a signaling-competent heterotrimeric complex. Here we present the crystal structure of IL-1β bound to its primary receptor IL-1RI and its receptor accessory protein IL-1RAcP, providing insight into how IL-1–type cytokines initiate signaling and revealing an evolutionary relationship with the fibroblast growth factor receptor family.

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Figure 1: Structural features of the IL-1β signaling complex.
Figure 2: Comparison of IL-1β and FGF signaling complexes.
Figure 3: The IL-1 cytokine receptor family interaction wheel.

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Protein Data Bank

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Protein Data Bank

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Acknowledgements

We thank the staff at the Advanced Light Source for their assistance. K.C.G. is an Investigator of the Howard Hughes Medical Institute and is supported by NIH grant R01-AI51321. C.T. was supported by a long-term postdoctoral fellowship from the International Human Frontier Science Program Organization.

Author information

K.C.G. conceived of the project, supervised the experiments and participated in writing the manuscript; J.F.B. contributed insights into the evolutionary relationships of the IL-1R activating complex to other receptors; C.T. executed the study and wrote the manuscript.

Correspondence to K Christopher Garcia.

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The authors declare no competing financial interests.

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Supplementary Text and Figures

Supplementary Figures 1–3, Supplementary Table 1, Supplementary Discussion and Supplementary Methods (PDF 1000 kb)

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