| 内容提要: |
The fibronectin type III domian (FN3) is a small autonmous folding unit. Due to its β-sandwich structure closely resembles that of immunoglobulin domain, recently, it has made many scientists focus on using FN3 as a scaffold for novel binding proteins. BLyS (B lymphocyte stimulator belonging to the TNF family) is a cell survival and maturation factor for B cells, and overproduction of BLyS is associated with systemic autoimmune disease. So finding a novel antagonist that have highly affinity to BLys have become an urgent methold to curing autoimmune disease. However, traditional immunogloulin scaffolding method have large MW, less stability and other disadvantages. In this study, the key amino acidsbetween Blys and its native receptors were identified by computer-aided modeling(CADD) technology, then replaced the loops of FN3 and tested the molecular binding ability of the recombinant protein for BLyS. In this study, we exchange the 9 amino acides in FN loop with the conserved DxL motif in BAFF natural recepters to investigate the new antagonist of BAFF. |