Top-down analysis of purified IL-38

Interleukin (IL)-1 family cytokines are essential for host defense at epithelial barriers. The IL-1 family member IL-33 was recently linked to stress granules (SGs). Formation of SGs and other biomolecular condensates is promoted by proteins containing low complexity regions (LCRs). Computational analysis predicted LCRs in six of the eleven IL-1 family members. Among these, IL-38 contained a long LCR including two amyloid cores. IL-38 localized to intracellular condensates in keratinocytes exposed to oxidative stress (OS) and formed OS-induced amyloid aggregates in cells and in vitro. Top-down proteomic analysis was performed on purified recombinant IL-38 protein to characterize the presence of possible disulfide bonds.