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JBC:赖氨酸甲基化负调节IFITM3的抗病毒功能

2013-10-23 伊文 中科院

赖氨酸抗病毒干扰素
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10月16日，国际学术期刊Journal of Biological Chemistry在线发表了中科院上海巴斯德研究所李斌课题组题为Negative Regulation of Interferon-Induced Transmembrane Protein 3 by SET7-

10月16日，国际学术期刊Journal of Biological Chemistry在线发表了中科院上海巴斯德研究所李斌课题组题为Negative Regulation of Interferon-Induced Transmembrane Protein 3 by SET7-mediated Lysine Monomethylation的研究论文。此项研究揭示了干扰素诱导的跨膜蛋白3（IFITM3）的第88位赖氨酸能够被单甲基化,并且该单甲基化可以抑制IFITM3的抗病毒功能。同时，IFITM3蛋白甲基化程度受到了病毒感染和细胞因子干扰素的正负调节。此次研究首次发现了作为抗RNA病毒一个重要的广谱性宿主限制性因子IFITM3赖氨酸单甲基化可以调节宿主限制性因子的抗病毒功能。

在李斌研究员、AndyTsun副研究员的指导下，单昭等研究人员利用串联亲和纯化的方法纯化出IFITM3复合体，并通过质谱分析鉴定出一系列IFITM3相互作用蛋白及其蛋白翻译后修饰位点，即IFITM3第88位赖氨酸的单甲基化(K88me1)。通过氨基酸序列比对及免疫共沉淀实验，研究人员发现了该IFITM3第88位赖氨酸受到甲基化酶SET7的翻译后修饰调节。通过蛋白过表达及基因表达下调实验，研究人员进一步发现了IFITM3-K88me1水平会随着病毒感染的进程不断上调，进而导致IFITM3抗病毒功能下降，而抗病毒细胞因子干扰素α处理宿主细胞则可以下调IFITM3-K88me1水平。本研究结果证实了病毒可以通过调节IFITM3蛋白的翻译后修饰即K88me1水平从而逃离宿主限制因子的约束。同时，在分子病毒学研究组韩青霖等同学的帮助下，研究人员发现了干扰素抑制水疱性口炎病毒（VSV）和流感病毒(IAV)的抗病毒功能受到了SET7蛋白负调节，并且该过程依赖于SET7对IFITM蛋白的甲基化修饰，该发现为宿主病原体相互作用的研究领域提供了新的思路。 

这项研究得到了疱疹病毒分子生物学研究组钱志康研究员等的大力支持和帮助，并取得国家自然科学基金委、中国科学院上海生命科学研究院优秀青年人才领域前沿项目及上海市科委青年科技启明星计划等项目的经费支持。 

原文检索：

Shan Z, Han Q, Nie J, Cao X, Chen Z, Yin S, Gao Y, Lin F, Zhou X, Xu K, Fan H, Qian Z, Sun B, Zhong J, Li B, Tsun A.Negative Regulation of Interferon-Induced Transmembrane Protein 3 by SET7-mediated Lysine Monomethylation.J Biol Chem. 2013 Oct 15.

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    2014-05-19 lily1616

    #JBC#

    0

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    2013-10-25 yahu

    #抗病毒#

    0

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    2013-10-25 12498768m13(暂无昵称)

    #FIT#

    0

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    2013-10-25 w363522455

    #赖氨酸#

    0