Structural and dynamic determinants of type I interferon receptor assembly and their functional interpretation.
Structural and dynamic determinants of type I interferon receptor assembly and their functional interpretation.
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DOI：
10.1111/imr.12001
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发表时间：
2012-11
影响因子：
8.7
通讯作者：
Schreiber G
中科院分区：
文献类型：
--
作者：
Piehler J;Thomas C;Garcia KC;Schreiber G
I型干扰素（IFN）形成同源细胞因子的网络，所述同源细胞因子结合至共享的异源二聚体细胞表面受体并参与激活先天性和适应性免疫应答的信号传导途径。IFN通过相同的细胞表面受体介导不同反应的能力一直是有争议的辩论的主题，并具有重要的医学意义。在过去的十年中，一个全面的洞察IFN识别的结构，能量学和动力学的两个受体亚基，以及详细的相关性与它们的功能特性的水平上的信号激活，基因表达，和生物反应。所有I型IFN在相同位点结合两个受体亚基，并形成结构非常相似的三元复合物。差异IFN活性被认为是由不同的寿命和配体亲和力对受体亚基，这决定了组装和动态的质膜中的信号复合物。我们提出了一个简单的模型，它解释了差异IFN活性的基础上快速内吞的信号复合物和负反馈机制干扰三元复合物组装。对信号通路以及内体信号传导和运输的更多了解将需要全面的理解，这最终将导致IFN的治疗应用具有更高的疗效。
Type I interferons (IFNs) form a network of homologous cytokines that bind to a shared, heterodimeric cell surface receptor and engage signaling pathways that activate innate and adaptive immune responses. The ability of IFNs to mediate differential responses through the same cell surface receptor has been subject of a controversial debate and has important medical implications. During the past decade, a comprehensive insight into the structure, energetics, and dynamics of IFN recognition by its two-receptor subunits, as well as detailed correlations with their functional properties on the level of signal activation, gene expression, and biological responses were obtained. All type I IFNs bind the two-receptor subunits at the same sites and form structurally very similar ternary complexes. Differential IFN activities were found to be determined by different lifetimes and ligand affinities toward the receptor subunits, which dictate assembly and dynamics of the signaling complex in the plasma membrane. We present a simple model, which explains differential IFN activities based on rapid endocytosis of signaling complexes and negative feedback mechanisms interfering with ternary complex assembly. More insight into signaling pathways as well as endosomal signaling and trafficking will be required for a comprehensive understanding, which will eventually lead to therapeutic applications of IFNs with increased efficacy.
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影响因子：
2.3
作者：
Dupont, SA;Goelz, S;Green, M
通讯作者：
Green, M
影响因子：
4.8
作者：
Dubois A;François C;Descamps V;Fournier C;Wychowski C;Dubuisson J;Castelain S;Duverlie G
通讯作者：
Duverlie G
DOI：
10.3109/08977194.2012.669382
发表时间：
2012-06
期刊：
Growth factors (Chur, Switzerland)
影响因子：
--
作者：
Fuchs SY
通讯作者：
Fuchs SY
影响因子：
5.7
作者：
Dagil, Robert;Knudsen, Maiken J.;Kragelund, Birthe B.
通讯作者：
Kragelund, Birthe B.
DOI：
10.1073/pnas.0903487106
发表时间：
2009-06-09
影响因子：
11.1
作者：
Cheon, HyeonJoo;Stark, George R.
通讯作者：
Stark, George R.