Structure and function of interleukin-17 family cytokines.
10.1007/s13238-011-1006-5
- Author:
Xiaoping ZHANG
1
;
Pornpimon ANGKASEKWINAI
;
Chen DONG
;
Hong TANG
Author Information
1. Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
- Publication Type:Journal Article
- MeSH:
Amino Acid Sequence;
Animals;
Conserved Sequence;
Cysteine;
Disulfides;
chemistry;
Humans;
Interleukin-17;
chemistry;
metabolism;
Molecular Sequence Data;
Protein Structure, Secondary;
Protein Structure, Tertiary;
Receptors, Interleukin;
metabolism
- From:
Protein & Cell
2011;2(1):26-40
- CountryChina
- Language:English
-
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.
