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

Abstract 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. Howe...

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Main Authors: Xuyuan Zhang, Pan Yang, Nan Wang, Jialong Zhang, Jingyun Li, Hao Guo, Xiangyun Yin, Zihe Rao, Xiangxi Wang, Liguo Zhang
Format: Article
Language:English
Published: Oxford University Press 2017-04-01
Series:Protein & Cell
Subjects:
Online Access:http://link.springer.com/article/10.1007/s13238-017-0405-7
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author Xuyuan Zhang
Pan Yang
Nan Wang
Jialong Zhang
Jingyun Li
Hao Guo
Xiangyun Yin
Zihe Rao
Xiangxi Wang
Liguo Zhang
author_facet Xuyuan Zhang
Pan Yang
Nan Wang
Jialong Zhang
Jingyun Li
Hao Guo
Xiangyun Yin
Zihe Rao
Xiangxi Wang
Liguo Zhang
author_sort Xuyuan Zhang
collection DOAJ
description Abstract 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.
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spelling doaj.art-5a97ebda52f245c29766143393ddccd32023-09-02T19:12:25ZengOxford University PressProtein & Cell1674-800X1674-80182017-04-018859060010.1007/s13238-017-0405-7The binding of a monoclonal antibody to the apical region of SCARB2 blocks EV71 infectionXuyuan Zhang0Pan Yang1Nan Wang2Jialong Zhang3Jingyun Li4Hao Guo5Xiangyun Yin6Zihe Rao7Xiangxi Wang8Liguo Zhang9Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of SciencesNational Laboratory of Macromolecules, Institute of Biophysics, Chinese Academy of SciencesNational Laboratory of Macromolecules, Institute of Biophysics, Chinese Academy of SciencesKey Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of SciencesKey Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of SciencesKey Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of SciencesKey Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of SciencesNational Laboratory of Macromolecules, Institute of Biophysics, Chinese Academy of SciencesNational Laboratory of Macromolecules, Institute of Biophysics, Chinese Academy of SciencesKey Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of SciencesAbstract 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.http://link.springer.com/article/10.1007/s13238-017-0405-7SCARB2EV71monoclonal antibodyHFMDreceptor
spellingShingle Xuyuan Zhang
Pan Yang
Nan Wang
Jialong Zhang
Jingyun Li
Hao Guo
Xiangyun Yin
Zihe Rao
Xiangxi Wang
Liguo Zhang
The binding of a monoclonal antibody to the apical region of SCARB2 blocks EV71 infection
Protein & Cell
SCARB2
EV71
monoclonal antibody
HFMD
receptor
title The binding of a monoclonal antibody to the apical region of SCARB2 blocks EV71 infection
title_full The binding of a monoclonal antibody to the apical region of SCARB2 blocks EV71 infection
title_fullStr The binding of a monoclonal antibody to the apical region of SCARB2 blocks EV71 infection
title_full_unstemmed The binding of a monoclonal antibody to the apical region of SCARB2 blocks EV71 infection
title_short The binding of a monoclonal antibody to the apical region of SCARB2 blocks EV71 infection
title_sort binding of a monoclonal antibody to the apical region of scarb2 blocks ev71 infection
topic SCARB2
EV71
monoclonal antibody
HFMD
receptor
url http://link.springer.com/article/10.1007/s13238-017-0405-7
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