Psoriasis pathogenesis – Pso p27 constitutes a compact structure forming large aggregates

• Pso p27 is generated from SerpinB3 by digestion with chymase with formation of three fragments.
• The terminal fragments remain associated with the Pso p27 core structure to make a Pso p27 complex
• Pso p27 complexes form large aggregates with unique Pso p27 epitopes exposed on the surface.

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.

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