Molecular mimicry between IL-33 and KSHV for attachment to chromatin through the H2A-H2B acidic pocket.
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.
Pubmed ID: 18688256 RIS Download
3T3 Cells | Amino Acid Motifs | Amino Acid Sequence | Animals | Antigens, Viral | Cell Line | Chromatin | Chromosomes, Human | Dimerization | Dogs | Herpesvirus 8, Human | Histones | Humans | Interleukin-33 | Interleukins | Mice | Mitosis | Molecular Mimicry | Molecular Sequence Data | Nuclear Proteins | Nucleosomes | Protein Binding | Protein Structure, Tertiary