title: Structural and functional comparison of cytokine interleukin-1 beta from chicken and human.
abstract: Interleukin-1 beta (IL-1β) is an important cytokine in the immune system. The properties of avian IL-1βs are less well understood than the mammalian IL-1βs, and there is no available structure of avian IL-1βs in the Protein Data Bank. Here, we report the crystal structures of wild-type and Y157F mutant IL-1βs from chicken. Both the wild-type and mutant IL-1βs share a beta-trefoil conformation similar to that of human IL-1β and also have an internal hydrophobic cavity. However, the cavity sizes clearly differ from that of human IL-1β due to the packing of hydrophobic residues. Our studies also reveal that the relative thermal stability of IL-1βs does not correlate with cavity size but rather is dependent on the amino acid residues present around the cavity. This cavity serves as a scaffold for maintaining the structure of the IL-1β core region but does not have a biological function per se. Moreover, we found that human IL-1β cannot induce chemokine expression in chicken fibroblasts or elevate plasma cortisol levels in chickens, implying a lack of cross-species bioactivity. Close examination reveals that significant structural and sequence differences occur in the terminal and some loop regions between human and chicken IL-1βs. These variable regions have been shown to be critical for receptor binding, thus resulting in a lack of species cross-reactivity between human and chicken IL-1β.
authors.affiliation: Institute of Bioinformatics and Structural Biology, and College of Life Sciences, National Tsing Hua University, Hsinchu 300, Taiwan.
authors.forename: Chao-Sheng
authors.initials: CS
authors.lastname: Cheng
authors.forename: Wen-Tin
authors.initials: WT
authors.lastname: Chen
authors.forename: Long-Huw
authors.initials: LH
authors.lastname: Lee
authors.forename: Yu-Wen
authors.initials: YW
authors.lastname: Chen
authors.forename: Shun-Ya
authors.initials: SY
authors.lastname: Chang
authors.forename: Ping-Chiang
authors.initials: PC
authors.lastname: Lyu
authors.forename: Hsien-Sheng
authors.initials: HS
authors.lastname: Yin
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D055592:Biophysical Phenomena; D018925:Chemokines / Q000235:genetics / Q000378:metabolism; D002645:Chickens / Q000097:blood / Q000276:immunology; D018360:Crystallography, X-Ray; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007118:Immunoassay; D053583:Interleukin-1beta / Q000737:chemistry* / Q000276:immunology*; D008969:Molecular Sequence Data; D050505:Mutant Proteins / Q000276:immunology; D025941:Protein Interaction Mapping; D011994:Recombinant Proteins / Q000737:chemistry / Q000276:immunology; D040681:Structural Homology, Protein; D013696:Temperature
chemical_list: D018925:Chemokines; D053583:Interleukin-1beta; D050505:Mutant Proteins; D011994:Recombinant Proteins; D006854:Hydrocortisone