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The binding of a monoclonal antibody to the apical region of SCARB2 blocks EV71 infection

机译:单克隆抗体与SCARB2顶端区域的结合可阻止EV71感染

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摘要

Entero virus 71 (EV71) causes hand, foot, and mouth disease (HFMD) and occasionally leads to severe neurological complications and even death. Scavenger receptor class B member 2 (SCARB2) is a functional receptor for EV71, that mediates viral attachment, internalization, and uncoating. However, the exact binding site of EV71 on SCARB2 is unknown. In this study, we generated a monoclonal antibody (mAb) that binds to human but not mouse SCARB2. It is named JL2, and it can effectively inhibit EV71 infection of target cells. Using a set of chimeras of human and mouse SCARB2, we identified that the region containing residues 77–113 of human SCARB2 contributes significantly to JL2 binding. The structure of the SCARB2-JL2 complex revealed that JL2 binds to the apical region of SCARB2 involving α-helices 2, 5, and 14. Our results provide new insights into the potential binding sites for EV71 on SCARB2 and the molecular mechanism of EV71 entry.Electronic supplementary materialThe online version of this article (doi:10.1007/s13238-017-0405-7) contains supplementary material, which is available to authorized users.
机译:肠病毒71(EV71)引起手足口病(HFMD),并偶尔导致严重的神经系统并发症甚至死亡。清除剂受体B类成员2(SCARB2)是EV71的功能性受体,介导病毒附着,内在化和脱壳。但是,EV71在SCARB2上的确切结合位点尚不清楚。在这项研究中,我们产生了一种单克隆抗体(mAb),该抗体与人而非鼠SCARB2结合。它被命名为JL2,可以有效抑制EV71对靶细胞的感染。使用一组人类和小鼠SCARB2的嵌合体,我们确定了包含人类SCARB2残基77–113的区域对JL2结合起了重要作用。 SCARB2-JL2复合物的结构表明,JL2与SCARB2的顶端区域结合,涉及α-螺旋2、5和14。我们的结果为SCARB2上EV71的潜在结合位点和EV71进入的分子机理提供了新见解。电子补充材料本文的在线版本(doi:10.1007 / s13238-017-0405-7)包含补充材料,授权用户可以使用。

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