title: Structure and function of interleukin-17 family cytokines.
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.
authors.affiliation: Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Zhang
authors.forename: Pornpimon
authors.initials: P
authors.lastname: Angkasekwinai
authors.forename: Chen
authors.initials: C
authors.lastname: Dong
authors.forename: Hong
authors.initials: H
authors.lastname: Tang
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017124:Conserved Sequence; D003545:Cysteine; D004220:Disulfides / Q000737:chemistry; D006801:Humans; D020381:Interleukin-17 / Q000737:chemistry* / Q000378:metabolism*; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D018123:Receptors, Interleukin / Q000378:metabolism
chemical_list: D004220:Disulfides; D020381:Interleukin-17; D018123:Receptors, Interleukin; D003545:Cysteine