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Crystal structures of interleukin 17A and its complex with IL-17 receptor A

Author

Listed:
  • Shenping Liu

    (Structural Biology and Biophysics Group, Pfizer Groton Laboratories)

  • Xi Song

    (Structural Biology and Biophysics Group, Pfizer Groton Laboratories)

  • Boris A. Chrunyk

    (Structural Biology and Biophysics Group, Pfizer Groton Laboratories)

  • Suman Shanker

    (Structural Biology and Biophysics Group, Pfizer Groton Laboratories)

  • Lise R. Hoth

    (Structural Biology and Biophysics Group, Pfizer Groton Laboratories)

  • Eric S. Marr

    (Structural Biology and Biophysics Group, Pfizer Groton Laboratories)

  • Matthew C. Griffor

    (Structural Biology and Biophysics Group, Pfizer Groton Laboratories)

Abstract

The constituent polypeptides of the interleukin-17 family form six different homodimeric cytokines (IL-17A–F) and the heterodimeric IL-17A/F. Their interactions with IL-17 receptors A–E (IL-17RA–E) mediate host defenses while also contributing to inflammatory and autoimmune responses. IL-17A and IL-17F both preferentially engage a receptor complex containing one molecule of IL-17RA and one molecule of IL-17RC. More generally, IL-17RA appears to be a shared receptor that pairs with other members of its family to allow signaling of different IL-17 cytokines. Here we report crystal structures of homodimeric IL-17A and its complex with IL-17RA. Binding to IL-17RA at one side of the IL-17A molecule induces a conformational change in the second, symmetry-related receptor site of IL-17A. This change favors, and is sufficient to account for, the selection of a different receptor polypeptide to complete the cytokine-receptor complex. The structural results are supported by biophysical studies with IL-17A variants produced by site-directed mutagenesis.

Suggested Citation

  • Shenping Liu & Xi Song & Boris A. Chrunyk & Suman Shanker & Lise R. Hoth & Eric S. Marr & Matthew C. Griffor, 2013. "Crystal structures of interleukin 17A and its complex with IL-17 receptor A," Nature Communications, Nature, vol. 4(1), pages 1-9, October.
    • Handle: RePEc:nat:natcom:v:4:y:2013:i:1:d:10.1038_ncomms2880
    DOI: 10.1038/ncomms2880
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