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.
Roussel
Lucie
L
CNRS, IPBS (Institute of Pharmacology and Structural Biology), 205 Route de Narbonne, F-31077 Toulouse, France.
Erard
Monique
M
Cayrol
Corinne
C
Girard
Jean-Philippe
JP
D016475:3T3 Cells; D020816:Amino Acid Motifs / Q000502:physiology; D000595:Amino Acid Sequence; D000818:Animals; D000956:Antigens, Viral / Q000737:chemistry / Q000378:metabolism; D002460:Cell Line; D002843:Chromatin / Q000378:metabolism*; D002877:Chromosomes, Human / Q000235:genetics; D019281:Dimerization; D004285:Dogs; D019288:Herpesvirus 8, Human / Q000737:chemistry* / Q000378:metabolism; D006657:Histones / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D000067596:Interleukin-33; D007378:Interleukins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008938:Mitosis / Q000235:genetics; D018716:Molecular Mimicry / Q000502:physiology*; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism; D009707:Nucleosomes / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary
D000956:Antigens, Viral; D002843:Chromatin; D006657:Histones; C506536:IL33 protein, human; D000067596:Interleukin-33; D007378:Interleukins; D009687:Nuclear Proteins; D009707:Nucleosomes; C109540:latency-associated nuclear antigen