AI Article Synopsis
- Cytokines from the interleukin (IL)-1 family play key roles in controlling immune and inflammatory responses, with the recently identified IL-36 family involved in conditions like psoriasis and arthritis.
- The study reveals that IL-36α interacts with heme, highlighting two specific heme-binding sites and providing structural insights through spectroscopy and NMR analysis.
- Findings suggest that heme negatively regulates IL-36 signaling in rheumatoid arthritis fibroblast cells, indicating that IL-1 cytokines may be influenced by heme, expanding our understanding of heme-binding proteins.
Article Abstract
Cytokines of the interleukin (IL)-1 family regulate immune and inflammatory responses. The recently discovered IL-36 family members are involved in psoriasis, rheumatoid arthritis, and pulmonary diseases. Here, we show that IL-36α interacts with heme thereby contributing to its regulation. Based on in-depth spectroscopic analyses, we describe two heme-binding sites in IL-36α that associate with heme in a pentacoordinated fashion. Solution NMR analysis reveals structural features of IL-36α and its complex with heme. Structural investigation of a truncated IL-36α supports the notion that the N-terminus is necessary for association with its cognate receptor. Consistent with our structural studies, IL-36-mediated signal transduction was negatively regulated by heme in synovial fibroblast-like synoviocytes from rheumatoid arthritis patients. Taken together, our results provide a structural framework for heme-binding proteins and add IL-1 cytokines to the group of potentially heme-regulated proteins.
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Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6858345 | PMC |
| http://dx.doi.org/10.1038/s41598-019-53231-0 | DOI Listing |
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