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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References
Sims, J.E. & Smith, D.E. Nat. Rev. Immunol. 10, 89–102 (2010).
Arend, W.P., Palmer, G. & Gabay, C. Immunol. Rev. 223, 20–38 (2008).
Wang, D. et al. Nat. Immunol. 11, 905–911 (2010).
Vigers, G.P., Anderson, L.J., Caffes, P. & Brandhuber, B.J. Nature 386, 190–194 (1997).
Murzin, A.G., Lesk, A.M. & Chothia, C. J. Mol. Biol. 223, 531–543 (1992).
Schreuder, H. et al. Nature 386, 194–200 (1997).
Venkataraman, G., Raman, R., Sasisekharan, V. & Sasisekharan, R. Proc. Natl. Acad. Sci. USA 96, 3658–3663 (1999).
Schlessinger, J. et al. Mol. Cell 6, 743–750 (2000).
Casadio, R. et al. FEBS Lett. 499, 65–68 (2001).
Kiselyov, V.V., Kochoyan, A., Poulsen, F.M., Bock, E. & Berezin, V. Protein Sci. 15, 2318–2322 (2006).
Kalinina, J. et al. Structure 20, 77–88 (2012).
Wass, M.N., David, A. & Sternberg, M.J. Curr. Opin. Struct. Biol. 21, 382–390 (2011).
Ehrlich, M., Horbelt, D., Marom, B., Knaus, P. & Henis, Y.I. Cell. Signal. 23, 1424–1432 (2011).
Wang, X., Lupardus, P., Laporte, S.L. & Garcia, K.C. Annu. Rev. Immunol. 27, 29–60 (2009).
Thomas, C. et al. Cell 146, 621–632 (2011).
Chen, H. et al. Proc. Natl. Acad. Sci. USA 105, 19660–19665 (2008).
Nyman, T. et al. J. Biol. Chem. 283, 11861–11865 (2008).
Ely, L.K., Fischer, S. & Garcia, K.C. Nat. Immunol. 10, 1245–1251 (2009).
Dinarello, C. et al. Nat. Immunol. 11, 973 (2010).
Boraschi, D. & Tagliabue, A. Vitam. Horm. 74, 229–254 (2006).
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.
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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.
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Supplementary Figures 1–3, Supplementary Table 1, Supplementary Discussion and Supplementary Methods (PDF 1000 kb)
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Thomas, C., Bazan, J. & Garcia, K. Structure of the activating IL-1 receptor signaling complex. Nat Struct Mol Biol 19, 455–457 (2012). https://doi.org/10.1038/nsmb.2260
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DOI: https://doi.org/10.1038/nsmb.2260
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