Molecular mimicry between IL-33 and KSHV for attachment to chromatin through the H2A-H2B acidic pocket |
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Authors: | Roussel Lucie Erard Monique Cayrol Corinne Girard Jean-Philippe |
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Affiliation: | CNRS, IPBS (Institute of Pharmacology and Structural Biology), 205 Route de Narbonne, F-31077 Toulouse, France. |
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Abstract: | Interleukin-33 (IL-33) is an IL-1-like ligand for the ST2 receptor that stimulates the production of Th2-associated cytokines. Recently, we showed that IL-33 is a chromatin-associated factor in the nucleus of endothelial cells in vivo. Here, we report the identification of a short IL-33 chromatin-binding peptide that shares striking similarities with a motif found in Kaposi sarcoma herpesvirus LANA (latency-associated nuclear antigen), which is responsible for the attachment of viral genomes to mitotic chromosomes. Similar to LANA, the IL-33 peptide docks into the acidic pocket formed by the H2A-H2B dimer at the nucleosomal surface and regulates chromatin compaction by promoting nucleosome-nucleosome interactions. Taken together, our data provide important new insights into the nuclear roles of IL-33, and show a unique example of molecular mimicry of a chromatin-associated cytokine by a DNA tumour virus. In addition, the data provide, to the best of our knowledge, the first demonstration of the existence of non-histone cellular factors that bind to the acidic pocket of the nucleosome. |
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Keywords: | chromatin cytokine histone IL-1 virus |
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