Volume 2 Issue 1
Jan.  2011
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Xiaoping Zhang, Pornpimon Angkasekwinai, Chen Dong, Hong Tang. Structure and function of interleukin-17 family cytokines[J]. Protein&Cell, 2011, 2(1): 26-40. doi: 10.1007/s13238-011-1006-5
Citation: Xiaoping Zhang, Pornpimon Angkasekwinai, Chen Dong, Hong Tang. Structure and function of interleukin-17 family cytokines[J]. Protein&Cell, 2011, 2(1): 26-40. doi: 10.1007/s13238-011-1006-5

Structure and function of interleukin-17 family cytokines

doi: 10.1007/s13238-011-1006-5
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Our work is supported by the National Basic Research Program (973 Program) (No. 2011CB946104) as well as the National Natural Science Foundation of China Key Research Grant (No. 31030031) to Hong Tang.

  • Received Date: 2010-12-28
  • Rev Recd Date: 2010-12-28
  • 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.
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