Pentraxins and Fc Receptor-Mediated Immune Responses.
Pentraxins and Fc Receptor-Mediated Immune Responses.
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DOI：
10.3389/fimmu.2018.02607
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发表时间：
2018
影响因子：
7.3
通讯作者：
Sun PD
中科院分区：
文献类型：
--
作者：
Lu J;Mold C;Du Clos TW;Sun PD
C 反应蛋白 (CRP) 是五聚蛋白家族的成员。这些蛋白质在进化过程中高度保守，早在 2.5 亿年前就已存在。哺乳动物五聚蛋白的特征是存在五个相同的非共价连接的亚基。每个亚基都有一个结构保守的钙依赖性配体结合位点。多年来建立的五聚蛋白的生物活性包括介导吞噬作用和补体激活的调理作用的能力。五聚蛋白在防止病原菌感染和调节炎症反应方面发挥着重要作用。人们很早就认识到其中一些功能是通过 C1q 激活经典补体途径介导的。然而，实验证据表明五聚蛋白的细胞受体也在吞噬作用中发挥作用。最近的实验证据表明五聚蛋白和 Fc 受体之间存在直接联系。 Fc 受体首先被确定为免疫球蛋白的主要受体。当多价配体与 IgG 结合位点相互作用并且信号通路的激活需要 Fc 受体交联时，IgG 复合物和 Fc 受体之间相互作用的亲和力大大增强。人五聚蛋白结合并激活人和小鼠 IgG 受体 FcγRI 和 FcγRII，以及人 IgA 受体 FcαRI。 Fc 受体与溶液中和细胞表面上的五聚蛋白之间相互作用的亲和力类似于抗体与低亲和力 Fc 受体的结合。晶体学和诱变研究已经确定了这些相互作用的结构特征，并确定了一对一结合的化学计量。五聚蛋白聚集或与多价配体的结合增加了结合的亲合力并导致这些受体的吞噬作用和细胞因子合成的激活。本综述将讨论五聚蛋白 Fc 受体相互作用的结构和功能特征及其对宿主防御和炎症的影响。
C-reactive protein (CRP) is a member of the pentraxin family of proteins. These proteins are highly conserved over the course of evolution being present as far back as 250 million years ago. Mammalian pentraxins are characterized by the presence of five identical non-covalently linked subunits. Each subunit has a structurally conserved site for calcium-dependent ligand binding. The biological activities of the pentraxins established over many years include the ability to mediate opsonization for phagocytosis and complement activation. Pentraxins have an important role in protection from infection from pathogenic bacteria, and regulation of the inflammatory response. It was recognized early on that some of these functions are mediated by activation of the classical complement pathway through C1q. However, experimental evidence suggested that cellular receptors for pentraxins also play a role in phagocytosis. More recent experimental evidence indicates a direct link between pentraxins and Fc receptors. The Fc receptors were first identified as the major receptors for immunoglobulins. The avidity of the interaction between IgG complexes and Fc receptors is greatly enhanced when multivalent ligands interact with the IgG binding sites and activation of signaling pathways requires Fc receptor crosslinking. Human pentraxins bind and activate human and mouse IgG receptors, FcγRI and FcγRII, and the human IgA receptor, FcαRI. The affinities of the interactions between Fc receptors and pentraxins in solution and on cell surfaces are similar to antibody binding to low affinity Fc receptors. Crystallographic and mutagenesis studies have defined the structural features of these interactions and determined the stoichiometry of binding as one-to-one. Pentraxin aggregation or binding to multivalent ligands increases the avidity of binding and results in activation of these receptors for phagocytosis and cytokine synthesis. This review will discuss the structural and functional characteristics of pentraxin Fc receptor interactions and their implications for host defense and inflammation.
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影响因子：
7.3
作者：
Jimenez RV;Wright TT;Jones NR;Wu J;Gibson AW;Szalai AJ
通讯作者：
Szalai AJ
影响因子：
--
作者：
Mold, Carolyn;Du Clos, Terry W.
通讯作者：
Du Clos, Terry W.
影响因子：
8
作者：
Lu, Jinghua;Marjon, Kristopher D.;Sun, Peter
通讯作者：
Sun, Peter
影响因子：
8.7
作者：
Lu J;Marjon KD;Mold C;Du Clos TW;Sun PD
通讯作者：
Sun PD
影响因子：
17.1
作者：
Castaño AP;Lin SL;Surowy T;Nowlin BT;Turlapati SA;Patel T;Singh A;Li S;Lupher ML Jr;Duffield JS
通讯作者：
Duffield JS