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中国团队研究发现细胞核内存在能特异性识别病毒DNA的分子

来源:科技日报 时间:2019-07-19 15:00:41

科技日报北京7月19日电 (记者张佳星)19日,《科学》杂志以研究长文(Research Article)的形式在线发表了中国工程院院士、南开大学校长曹雪涛课题组的研究,研究发现细胞核内存在能特异性识别病毒DNA的天然免疫受体分子,可启动对病毒的“强反击”。

整个全新机制的关键是一种被称为异质性细胞核核糖蛋白A2B1(hnRNP-A2B1)的蛋白分子。“用‘民兵’来形容hnRNP-A2B1再合适不过,它在平时是‘民’,负责转运mRNA,遇到病毒攻击的战时,就变成‘兵’,通过蛋白‘聚变’、甲基化等变化从细胞核内移位到细胞质激活天然免疫信号通路、启动抗病毒效应。”曹雪涛说。

曹雪涛院士与博士后王蕾、医学免疫学国家重点实验室讲师温明岳一起,先锁定关键病毒DNA识别分子,随后逐步“牵出”激活免疫功能的细胞通路。

团队首先用生物素标记的病毒DNA作为“钓饵”,从细胞核提取物中“钓”出DNA结合蛋白,进行质谱鉴定和二维电泳筛选,进一步锁定细胞核内能够在病毒感染之后移位到细胞质中的蛋白分子,通过一系列细胞功能与动物试验,从23个候选分子中,最终鉴定出hnRNPA2B1是一个关键的核内DNA天然免疫识别受体。

随后团队弄清了蛋白从“民”到“兵”的升华过程:其是二聚化(2个分子聚合)后,在第226位精氨酸位点发生了去甲基化。“武装”之后的识别分子会从细胞核移动到细胞质中激活干扰素表达的相关通路。团队还发现hnRNPA2B1能够促进cGAS、IFI16、STING等DNA识别受体mRNA的m6A修饰及出核,从而放大和增强这些细胞质中的已知天然免疫分子的效能。

该发现揭示了细胞核内的蛋白分子参与天然免疫识别及其信号转导的新机制,为抗病毒治疗与炎症疾病防治提供了新思路和潜在药物研发新靶标。

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