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

Abstract

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.

Brown Spider (Loxosceles) Venom Toxins as Potential Biotools for the Development of Novel Therapeutics

“…Human serpins are the most well-characterized serine protease inhibitors because they have a central role in several physiologic processes such as coagulation, fibrinolysis, development, malignancy, inflammation, and fertilization. Serpins inhibit a variety of circulating proteases as well as proteases that are activated or released in tissue, the reason why these molecules are involved in different pathologies and dysfunctions [86,87,88]. For instance, serpinopathies can occur due to genetic mutations that lead to inactivation of serpins by protein aggregation with loss of function [89].…”

Proteomics in Psoriasis

“…This study underscores the benefit of using an animal model in screening for changes in the skin proteome that finally led to identification of novel proteins involved in psoriasis [ 28 ]. Lysvand et al [ 29 ] applied blue native gel electrophoresis and MALDI-TOF/TOF MS/MS to analyze protein complexes in the psoriatic scale and showed that post-translational modification (cleavage) of SerpinB3 (SCCA1) caused unique epitopes on the Pso p27 complex that may be responsible for the immunogenicity of such complex in psoriasis. Swindell et al [ 30 ] utilized label-free, gel-enhanced LC-MS/MS (GeLC-MS/MS), LTQ-Orbitrap-nanoLC-MS/MS to compare protein expression in lesional vs. non-lesional skins from 14 psoriatic patients and found that 748 proteins had differential levels between the two groups, including those with concordant and discordant mRNA changes, most of which were targeted by interleukin-17A (IL-17A).…”