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

The binding of a monoclonal antibody to the apical region of SCARB2 blocks EV71 infection.
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单克隆抗体与 SCARB2 顶端区域的结合可阻断 EV71 感染

DOI:
10.1007/s13238-017-0405-7
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发表时间:
2017-08
期刊:
影响因子:
21.1
通讯作者:
Zhang L
Zhang L
中科院分区:
生物学1区
文献类型:
--
作者:
Zhang X;Yang P;Wang N;Zhang J;Li J;Guo H;Yin X;Rao Z;Wang X;Zhang L

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肠道病毒71(EV 71)引起手足口病(HFMD),偶尔会导致严重的神经系统并发症,甚至死亡。清道夫受体B类成员2(SCARB 2)是EV 71的功能性受体,其介导病毒附着、内化和脱壳。然而,EV 71在SCARB 2上的确切结合位点是未知的。在这项研究中,我们产生了一种单克隆抗体(mAb),结合人,但不小鼠SCARB 2。它被命名为JL 2,它可以有效地抑制EV 71感染靶细胞。使用一组人和小鼠SCARB 2的嵌合体,我们鉴定了包含人SCARB 2的残基77-113的区域显著地有助于JL 2结合。SCARB 2-JL 2复合物的结构显示,JL 2与SCARB 2的顶端区域结合,涉及α-螺旋2、5和14。我们的研究结果为EV 71在SCARB 2上的潜在结合位点和EV 71进入的分子机制提供了新的见解。本文的在线版本(doi:10.1007/s13238-017-0405-7)包含补充材料,可供授权用户使用。
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. The online version of this article (doi:10.1007/s13238-017-0405-7) contains supplementary material, which is available to authorized users.
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