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.