Crystal structures for short-chain pentraxin from zebrafish demonstrate a cyclic trimer with new recognition and effector faces
Crystal structures for short-chain pentraxin from zebrafish demonstrate a cyclic trimer with new recognition and effector faces
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斑马鱼短链五聚蛋白的晶体结构展示了具有新识别和效应面的环状三聚体
DOI：
10.1016/j.jsb.2015.01.001
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发表时间：
2015-03-01
影响因子：
3
通讯作者：
Xia, Chun
中科院分区：
文献类型：
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作者：
Chen, Rong;Qi, Jianxun;Xia, Chun
短链五聚蛋白（PTXs），包括C反应蛋白（CRP）和血清淀粉样蛋白P（SAP），是先天性模式识别受体，它们通过C1q触发经典补体途径，在识别和清除各种病原菌方面发挥着至关重要的作用。与抗体类似，五聚蛋白也可通过与Fc受体（FcRs）相互作用激活调理作用和吞噬作用。对人五聚蛋白已进行了各种结构研究，但尚无关于硬骨鱼五聚蛋白晶体结构的报道。在此，我们展示了斑马鱼PTX（Dare - PTX - Ca和Dare - PTX）的晶体结构。Dare - PTX - Ca和Dare - PTX均为环状三聚体，这是结晶五聚蛋白的新形式。这些结构表明，Dare - PTX识别面上的配体结合口袋（LBP）深而窄。同源建模显示，来自不同Dare - PTX基因座的LBP在形状上存在差异，反映了它们的特异性识别能力。此外，与人类C反应蛋白（hCPR）的结构相比，在Dare - PTX中发现了一种新的C1q结合模式。另外，人类血清淀粉样蛋白P（hSAP）的FcR结合位点在Dare - PTX中部分保守。这些结果将有助于理解大约4.5亿年前进化而来的硬骨鱼中的原始五聚蛋白。（C）2015爱思唯尔公司。保留所有权利。
Short-chain pentraxins (PTXs), including CRP and SAP, are innate pattern recognition receptors that play vital roles in the recognition and elimination of various pathogenic bacteria by triggering the classical complement pathway through C1q. Similar to antibodies, pentraxins can also activate opsonisation and phagocytosis by interacting with Fc receptors (FcRs). Various structural studies on human PTXs have been performed, but there are no reports about the crystal structure of bony fish pentraxins. Here, the crystal structures of zebrafish PTX (Dare-PTX-Ca and Dare-PTX) are presented. Both Dare-PTX-Ca and Dare-PTX are cyclic trimers, which are new forms of crystallised pentraxins. The structures reveal that the ligand-binding pocket (LBP) in the recognition face of Dare-PTX is deep and narrow. Homology modelling shows that LBPs from different Dare-PTX loci differ in shape, reflecting their specific recognition abilities. Furthermore, in comparison with the structure of hCPR, a new C1q binding mode was identified in Dare-PTX. In addition, the FcR-binding sites of hSAP are partially conserved in Dare-PTX. These results will shed light on the understanding of a primitive PTX in bony fish, which evolved approximately 450 million years ago. (C) 2015 Elsevier Inc. All rights reserved.