Abstract
Interleukin-1α is one of the members of signaling transduction molecules which serves diverse biological functions. It is secreted by the cell through the non-classical pathway and interacts with the receptor on the cell surface to trigger the signal transduction cascade. It could induce fever, stimulate hepatic acute-phase protein production, augment lymphocyte responses, induce degenerative changes in joints and increase the numbers of bone marrow cells etc. It is also able to induce the release of several kinds of hypothalamic and pituitary peptides and to enhance the transcription of insulin. IL-1α thus plays an important role in human body and is the primary element to cause rheumatic arthritis and degeneration arthritis. In the thesis, the solution structure of IL-1α was solved using multi-dimensional nuclear magnetic resonance technology. First, the backbone information of the IL-1α was determined from a variety of 3D NMR experiments such as HNCA, HN(CO)CA, and HNCO, followed by other experiments such as CBCA(CO)NH, CBCANH, HBHA(CO)NH, and HCCH-TOCSY to determine the side-chain constraints of IL-1α. The 1H, 15N, 13C chemical shifts of 95% amino acid of IL-1α were successfully assigned. The solution structure of IL-1α was calculated by Aria/CNS software program using the NOE constraints obtained from 15N & 13C-edited NOESY experiments. The other constraints such as dihedral angle, hydrogen bond, chemical shift index were also used for structure calculation etc. The 3D solution structure of IL-1α determined in the present study can help us to understand the non-classical pathway of IL-1α.