Lysvand Hilde, Helland Ronny, Hagen Lars, Slupphaug Geir, Iversen Ole-Jan
Department of Laboratory Medicine, Children's and Women's Health, Faculty of Medicine, Norwegian University of Science and Technology, NTNU, Postbox 8905, N-7491 Trondheim, Norway.
Department of Chemistry, Norwegian Structural Biology Centre, Faculty of Science and Technology, University of Tromsø, Tromsø, Norway.
Biochem Biophys Rep. 2015 Jun 9;2:132-136. doi: 10.1016/j.bbrep.2015.06.001. eCollection 2015 Jul.
Psoriasis is a chronic inflammatory skin disease. The absence of microbial organisms as potential causal agents has given rise to the hypothesis that the inflammation is due to an autoimmune reaction. The defined inflamed areas of the skin lesions argue for an immunological disease with a local production of a causal antigen. Pso p27 is a protein generated in mast cells in psoriatic plaques, but not in uninvolved skin. We recently demonstrated that the Pso p27 is generated by cleavage of SerpinB3 (SCCA1) in the presence of mast cell associated chymase. In this communication we demonstrate by X-ray crystallographic analysis that the cleavage products associate into a complex similar to SCCA1, but with the reactive centre loop inserted into a 5-stranded central β-sheet. Native gel electrophoresis show that these Pso p27 complexes form large aggregates which may be of significance with respect to an immunogenic role of Pso p27.
银屑病是一种慢性炎症性皮肤病。由于缺乏作为潜在致病因子的微生物,从而产生了炎症是由自身免疫反应引起的假说。皮肤病变的明确炎症区域表明这是一种免疫性疾病,局部会产生致病抗原。Pso p27是一种在银屑病斑块的肥大细胞中产生的蛋白质,但在未受累皮肤中则不会产生。我们最近证明,Pso p27是在肥大细胞相关糜蛋白酶存在的情况下,由丝氨酸蛋白酶抑制剂B3(SCCA1)裂解产生的。在本通讯中,我们通过X射线晶体学分析证明,裂解产物形成了一种类似于SCCA1的复合物,但反应中心环插入到了一个由5条链组成的中央β折叠中。非变性凝胶电泳显示,这些Pso p27复合物形成了大聚集体,这可能与Pso p27的免疫原性作用有关。