Sci Signal:肿瘤坏死因子超级家族信号传递的结构基础

2018-01-08 药明康德 学术经纬

肿瘤坏死因子(tumor necrosis factor, TNF) 配体和受体超级家族在细胞增殖、存活和死亡方面起到重要作用。

肿瘤坏死因子(tumor necrosis factor, TNF) 配体和受体超级家族在细胞增殖、存活和死亡方面起到重要作用。激活或者抑制TNF超级家族信号通路可能对多种疾病具有治疗作用,其中包括癌症、自身免疫疾病和传染病。麻省总医院和哈佛医学院 (Massachusetts General Hospital and Harvard Medical School) 的科学家们对TNF超级家族配体和受体的结构和它们之间的相互作用进行了盘点。现有研究表明,一个三聚体配体和三个受体组成基本的信号传递单元,在这个单元中每个受体与两个配体单体构成的界面相结合。多个受体亚基的聚集是有效信号传递的前提。目前的研究认为受体在细胞膜上预先排列形成由反平行二聚体 (antiparallel dimers) 构成的大六边形结构。在这种构象时受体处于不能传递信号的静默状态。受体的激活需要配体的结合,激活性的交联抗体能够将受体结构稳定在传递信号的激活状态。反之,拮抗性抗体可以将受体构象固定在反平行二聚体状态,这可以有效阻断信号传递。这一结构模型可能帮助设计更有效地靶向TNF信号通路的疗法。

原始出处:

Eva S. Vanamee and Denise L. Faustman.Structural principles of tumor necrosis factor superfamily signaling.Sci Signal.  02 Jan 2018:Vol. 11, Issue 511, eaao4910.

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    2018-05-30 楚秀娟
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    2018-05-19 yaanren
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    2018-01-10 millore
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    2018-01-08 戒馋,懒,贪

    谢谢分享学习了

    0

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