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IL‐17s adopt a cystine knot fold: structure and activity of a novel cytokine, IL‐17F, and implications for receptor binding
Author(s) -
Hymowitz Sarah G.,
Filvaroff Ellen H.,
Yin JianPing,
Lee James,
Cai Liping,
Risser Philip,
Maruoka Miko,
Mao Weiguang,
Foster Jessica,
Kelley Robert F.,
Pan Guohua,
Gurney Austin L.,
de Vos Abraham M.,
Starovasnik Melissa A.
Publication year - 2001
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/20.19.5332
Subject(s) - biology , proinflammatory cytokine , microbiology and biotechnology , cytokine , receptor , genetics , immunology , inflammation
The proinflammatory cytokine interleukin 17 (IL‐17) is the founding member of a family of secreted proteins that elicit potent cellular responses. We report a novel human IL‐17 homolog, IL‐17F, and show that it is expressed by activated T cells, can stimulate production of other cytokines such as IL‐6, IL‐8 and granulocyte colony‐stimulating factor, and can regulate cartilage matrix turnover. Unexpectedly, the crystal structure of IL‐17F reveals that IL‐17 family members adopt a monomer fold typical of cystine knot growth factors, despite lacking the disulfide responsible for defining the canonical ‘knot’ structure. IL‐17F dimerizes in a parallel manner like neurotrophins, and features an unusually large cavity on its surface. Remarkably, this cavity is located in precisely the same position where nerve growth factor binds its high affinity receptor, TrkA, suggesting further parallels between IL‐17s and neurotrophins with respect to receptor recognition.