Abstract
Interleukin-1 (IL-1) is an important factor in the inflammatory response and it involves in the various cellular activities including cell proliferation, differentiation and apoptosis. The IL-1 family contains two agonists (IL-1α and IL-1β) and a specific antagonist (IL-1 receptor antagonist, IL-1Ra). Also, IL-1α and IL-1β can be synthesized in the different cell lines such as monocytes, macrophages, neutrophils and hepatocytes. In circulation system, the major component of IL-1 is IL-1β. IL-1 has been proved to act as a potential vaccine adjuvant to active T cell and enhance antibody production. However, only the structures of human and murine IL-1s have been solved. Therefore, the crystal structure of chicken IL-1β would be determined to provide insight into this atomic structure for its medical application. In this study, the cDNA of chicken IL-1β was first cloned into pET28a vector and then expressed in E. coli BL21. The high resolution diffraction data of chicken IL-1β was collected from the BL13B1 beamline in NSRRC. The resolution of our crystal was up to 1.79 angstrom and the space group was P212121. The crystal structure was determined by molecular replacement (MR) method. The overall structure of chicken IL-1β is composed of 12 β-strands and one α-helix to form a barrel-shaped conformation. The electron density map in residues 36-41 & 55-64 is unable to be apparently observed, implying these regions have the high flexibility. According to the previous report, these two regions are critical for IL-1 receptor association. Therefore, the high flexibility in these regions is required to alter the local conformation and trigger the protein-protein interaction. Besides, the existence of an internal hydrophobic cavity in IL-1β is important for the protein stability. These residues around the cavity are highly conserved in human or murine. However, several conserved residues were not found in the cavity of chicken IL-1 and its residue packing pattern is also unique. Our studies also reveal that chicken IL-1 has the novel biophysical properties, which is not observed in other IL-1s.