Molecular mimicry between IL-33 and KSHV for attachment to chromatin through the H2A-H2B acidic pocket
Molecular mimicry between IL-33 and KSHV for attachment to chromatin through the H2A-H2B acidic pocket
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DOI：
10.1038/embor.2008.145
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发表时间：
2008-09-01
期刊：
影响因子：
7.7
通讯作者：
Girard, Jean-Philippe
中科院分区：
文献类型：
--
作者：
Roussel, Lucie;Erard, Monique;Girard, Jean-Philippe
Interleukin-33 (IL-33) 是 ST2 受体的 IL-1 样配体，可刺激 Th2 相关细胞因子的产生。最近，我们发现IL-33是体内内皮细胞核中的染色质相关因子。在这里，我们报告了一种短的 IL-33 染色质结合肽的鉴定，该肽与卡波西肉瘤疱疹病毒 LANA（潜伏相关核抗原）中发现的基序具有惊人的相似性，该基序负责将病毒基因组附着到有丝分裂染色体上。与 LANA 类似，IL-33 肽停靠在核小体表面 H2A-H2B 二聚体形成的酸性口袋中，并通过促进核小体-核小体相互作用来调节染色质压实。总而言之，我们的数据为 IL-33 的核作用提供了重要的新见解，并展示了 DNA 肿瘤病毒对染色质相关细胞因子进行分子模拟的独特例子。此外，据我们所知，这些数据首次证明了与核小体酸性口袋结合的非组蛋白细胞因子的存在。
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.