Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Crystal structure of the type-I interleukin-1 receptor complexed with interleukin-1β


Interleukin-1 (IL-1) is an important mediator of inflammatory disease. The IL-1 family currently consists of two agonists, IL-1α and IL-lβ, and one antagonist, IL-1ra. Each of these molecules binds to the type I IL-1 receptor (IL1R)1. The binding of IL-1α or IL-1β to IL1R is an early step in IL-1 signal transduction and blocking this interaction may therefore be a useful target for the development of new drugs. Here we report the three-dimensional structure of IL-1β bound to the extracellular domain of IL1R (s-IL1R) at 2.5Å resolution. IL-1β binds to s-IL1R with a 1:1 stoichiometry. The crystal structure shows that s-IL1R consists of three immunoglobulin-like domains which wrap around IL-1β in a manner distinct from the structures of previously described cytokine–receptor complexes. The two receptor-binding regions on IL-1β identified by site-directed mutagenesis2,3 both contact the receptor: one binds to the first two domains of the receptor, while the other binds exclusively to the third domain.

This is a preview of subscription content

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.


  1. 1

    Dinarello, C. A. Biologic basis for interleukin-1 in disease. Blood 87, 2095–2147 (1996).

    CAS  Google Scholar 

  2. 2

    Labriola-Thompkins, E. et al. Identification of the discontinuous binding site in human interleukin 1β for the type I interleukin 1 receptor. Proc. Natl Acad. Sci. USA 88, 11182–11186 (1991).

    ADS  Article  Google Scholar 

  3. 3

    Evans, R. J. et al. Mapping receptor binding sites in interleukin (IL)-l receptor antagonist and IL-1β by site-directed mutagenesis. J. Biol. Chem. 270, 11477–11483 (1995).

    CAS  Article  Google Scholar 

  4. 4

    Sims, J. E. et al. Cloning the interleukin 1 receptor from human T cells. Proc. Natl Acad. Sci. USA 86, 8946–8950 (1989).

    ADS  CAS  Article  Google Scholar 

  5. 5

    Vigers, G. P. A. et al. X-ray structure of interleukin-1 receptor antagonist at 2.0 Å resolution. J. Biol. Chem. 269, 12874–12879 (1994).

    CAS  PubMed  Google Scholar 

  6. 6

    Bork, P., Holm, L. & Sander, C. The immunoglobulin fold. Structural classification, sequence patterns and common core. J. Mol. Biol. 242, 309–320 (1994).

    CAS  Google Scholar 

  7. 7

    Shapiro, L. et al. Structural basis of cell-cell adhesion by cadherins. Nature 374, 327–337 (1995).

    ADS  CAS  Article  Google Scholar 

  8. 8

    Priestle, J. P., Schaer, H. P. & Gruetter, M. G. Crystallographic refinement of interleukin 1 beta at 2.0 Å resolution. Proc. Natl Acad. Sci. USA 86, 9667–9671 (1989).

    ADS  CAS  Article  Google Scholar 

  9. 9

    Walter, M. R. et al. Crystal structure of a complex between interferon-γ and its soluble high-affinity receptor. Nature 376, 230–235 (1995).

    ADS  CAS  Article  Google Scholar 

  10. 10

    de Vos, A. M., Ultsch, M. & Kossiakoff, A. A. Human growth hormone and extracellular domain of its receptor: crystal structure of the complex. Science 255, 306–312 (1992).

    ADS  CAS  Article  Google Scholar 

  11. 11

    Livnah, O. et al. Functional mimicry of a protein hormone by a peptide agonist: the EPO receptor complex at 2.8 Å. Science 273, 464–471 (1996).

    ADS  CAS  Article  Google Scholar 

  12. 12

    Banner, D. W. et al. Crystal structure of the soluble human 55 kd TNF receptor-human TNF beta complex: implications for TNF receptor activation. Cell 73, 431–445 (1993).

    CAS  Article  Google Scholar 

  13. 13

    Greenfeder, S. A. et al. Molecular cloning and characterization of a second subunit of the interleukin 1 receptor complex. J. Biol. Chem. 270, 1357–13765 (1995).

    Google Scholar 

  14. 14

    Otwinowski, Z. in Data Collection and Processing (eds Sawyer, L., Isaacs, N. & Bailey, S.) (SERC Daresbury Laboratory, Warrington, UK, 1993).

    Google Scholar 

  15. 15

    CCP4: Collaborative Computational Project No 4, Daresbury UK. Acta Crystallogr. D 50, 760 (1994).

  16. 16

    Jones, T. A., Zou, J. Y., Cowan, S. W. & Kjeldgaard, M. Improved methods for binding protein models in electron density maps and the location of errors in these models. Acta Crystallogr. A 47, 110–119 (1991).

    Article  Google Scholar 

  17. 17

    Brunger, A. T., Kuriyan, J. & Karplus, M. Crystallographic R factor refinement by molecular dynamics. Science 235, 458–460 (1987).

  18. 18

    Lee, B. & Richards, F. M. The interpretation of protein structures: estimation of static accessibility. J. Mol. Biol. 55, 379–400 (1971).

    CAS  Article  Google Scholar 

  19. 19

    Evans, S. V. SETOR: hardware-lighted three-dimensional solid model representations of macromolecules. J. Mol. Graphics 11, 134–138 (1993).

    CAS  Article  Google Scholar 

Download references

Author information



Rights and permissions

Reprints and Permissions

About this article

Cite this article

Vigers, G., Anderson, L., Caffes, P. et al. Crystal structure of the type-I interleukin-1 receptor complexed with interleukin-1β. Nature 386, 190–194 (1997).

Download citation

Further reading


By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing