Pentraxins and IgA share a binding hot-spot on FcαRI
Pentraxins and IgA share a binding hot-spot on FcαRI
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DOI：
10.1002/pro.2419
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发表时间：
2014-04-01
期刊：
影响因子：
8
通讯作者：
Sun, Peter
中科院分区：
文献类型：
--
作者：
Lu, Jinghua;Marjon, Kristopher D.;Sun, Peter
五聚蛋白、C反应蛋白（CRP）和血清淀粉样蛋白P组分（SAP）先前已被证明通过与Fc受体相互作用发挥先天调理素的功能。通过SAP与FcRIIA复合物的晶体结构阐明了这些相互作用的分子细节。最近，正五肽显示出结合并激活伊加的受体FcRI（CD 89）。在这里，我们使用基于对接模型的受体突变来进一步检查FcRI对五聚环肽的识别。正五肽与6个FcRI丙氨酸簇突变体的溶液结合显示，D1结构域的C链和F链上的突变Y35 A和R82 A分别显著降低了与CRP和SAP的受体结合。这些残基位于受体的IgA结合位点，因此显著影响受体与伊加的结合。FcRI上共有的五聚环蛋白和IgA结合位点进一步得到溶液结合竞争测定结果的支持。除了IgA结合位点之外，正五聚蛋白似乎与受体的更广泛区域相互作用，因为C链中的突变（R48 A/E49 A）增强了正五聚蛋白结合。与Fc受体不同，D2结构域的BC环和FG环上的H129 A/I130 A和R178 A突变分别对FcRI与正五肽的结合几乎没有影响。总之，我们的数据表明，pentraxins识别FcRI上的伊加相似的网站。
The pentraxins, C-reactive protein (CRP), and serum amyloid P component (SAP) have previously been shown to function as innate opsonins through interactions with Fc receptors. The molecular details of these interactions were elucidated by the crystal structure of SAP in complex with FcRIIA. More recently, pentraxins were shown to bind and activate FcRI (CD89), the receptor for IgA. Here, we used mutations of the receptor based on a docking model to further examine pentraxin recognition by FcRI. The solution binding of pentraxins to six FcRI alanine cluster mutants revealed that mutations Y35A and R82A, on the C-and F-strands of the D1 domain, respectively, markedly reduced receptor binding to CRP and SAP. These residues are in the IgA-binding site of the receptor, and thus, significantly affected receptor binding to IgA. The shared pentraxin and IgA-binding site on FcRI is further supported by the results of a solution binding competition assay. In addition to the IgA-binding site, pentraxins appear to interact with a broader region of the receptor as the mutation in the C-strand (R48A/E49A) enhanced pentraxin binding. Unlike Fc receptors, the H129A/I130A and R178A mutations on the BC- and FG-loops of D2 domain, respectively, had little effect on FcRI binding to the pentraxins. In conclusion, our data suggest that the pentraxins recognize a similar site on FcRI as IgA.