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. 2011 Feb 20;2(1):26–40. doi: 10.1007/s13238-011-1006-5

Structure and function of interleukin-17 family cytokines

Xiaoping Zhang 1,4, Pornpimon Angkasekwinai 2,3, Chen Dong 3,✉, Hong Tang 1,✉
PMCID: PMC4875287  PMID: 21337007

Abstract

The recently identified interleukin-17 (IL-17) cytokines family, which comprises six members in mammals (IL-17A-F), plays essential roles in the host immunity against infectious diseases and chronic inflammatory diseases. The three-dimensional structures containing IL-17A or IL-17F have become available and revealed the unique structural features of IL-17s as well as their receptors. Molecular modeling in this review shows that IL-17s may adopt a “cysteine knot” fold commonly seen in nerve growth factor (NGF) and other neurotrophins. Further modeling analysis unmasks a signature interaction feature of the IL-17F/IL-17RA complex, where a small loop of IL-17RA slots into the deep groove of the interface of IL-17F homodimer. This is quite different from the interaction between the best known four-helix cytokines and their cognate receptors. On the other hand, structure of IL-17A and its monoclonal antibody (CAT-2200) shows that, albeit that the antigenic epitope of IL-17A resides outside of the IL-17A homodimer interface, its physical proximity to the receptor binding groove may explain that antibody blockage would be achieved by interfering with the ligand-receptor interaction. This review is to summarize the advance in understanding the structure and function of IL-17 family cytokines, focusing mainly on IL-17A, IL-17F and IL-17E, in the hope of gaining better knowledge of immunotherapeutic strategies against various inflammatory diseases.

Electronic Supplementary Material

Supplementary material is available for this article at 10.1007/s13238-011-1006-5 and is accessible for authorized users.

Keywords: interleukin-17, cytokines, crystal structure, immunology

Electronic supplementary material

13238_2011_1006_MOESM1_ESM.pdf (336.4KB, pdf)

Supplementary material, approximately 336 KB.

Footnotes

These authors contributed equally to the work.

Electronic Supplementary Material

Supplementary material is available for this article at 10.1007/s13238-011-1006-5 and is accessible for authorized users.

Contributor Information

Chen Dong, Email: cdong@mdanderson.org.

Hong Tang, Email: tanghong@moon.ibp.ac.cn.

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