单克隆抗体与SCARB2顶端区域的结合可阻断肠道病毒71型（EV71）的感染。
The binding of a monoclonal antibody to the apical region of SCARB2 blocks EV71 infection.
作者信息
Zhang Xuyuan, Yang Pan, Wang Nan, Zhang Jialong, Li Jingyun, Guo Hao, Yin Xiangyun, Rao Zihe, Wang Xiangxi, Zhang Liguo
机构信息
Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
University of Chinese Academy of Sciences, Beijing, 100049, China.
出版信息
Protein Cell. 2017 Aug;8(8):590-600. doi: 10.1007/s13238-017-0405-7. Epub 2017 Apr 26.
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.
肠道病毒71型（EV71）可引起手足口病（HFMD），偶尔会导致严重的神经并发症甚至死亡。清道夫受体B类成员2（SCARB2）是EV71的功能性受体，介导病毒的附着、内化和脱壳。然而，EV71在SCARB2上的确切结合位点尚不清楚。在本研究中，我们制备了一种单克隆抗体（mAb），该抗体可与人而非小鼠的SCARB2结合。它被命名为JL2，并且能够有效抑制EV71对靶细胞的感染。通过使用一组人源和鼠源SCARB2的嵌合体，我们确定人源SCARB2中包含第77 - 113位残基的区域对JL2的结合有显著贡献。SCARB2 - JL2复合物的结构表明，JL2结合于SCARB2的顶端区域，该区域涉及α螺旋2、5和14。我们的结果为EV71在SCARB2上的潜在结合位点以及EV71进入细胞的分子机制提供了新的见解。
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