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.
Keywords:
EV71; HFMD; SCARB2; monoclonal antibody; receptor.
MeSH terms
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Amino Acid Sequence
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Animals
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Antibodies, Monoclonal / chemistry*
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Antibodies, Monoclonal / genetics
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Antibodies, Monoclonal / metabolism
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Binding Sites
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Cell Line
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Crystallography, X-Ray
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Enterovirus A, Human / drug effects*
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Enterovirus A, Human / genetics
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Enterovirus A, Human / growth & development
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Enterovirus A, Human / immunology
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Fibroblasts / drug effects
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Fibroblasts / virology
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Gene Expression
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HEK293 Cells
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Humans
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Immunoglobulin Fab Fragments / chemistry*
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Immunoglobulin Fab Fragments / genetics
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Immunoglobulin Fab Fragments / metabolism
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Lysosomal Membrane Proteins / chemistry*
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Lysosomal Membrane Proteins / genetics
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Lysosomal Membrane Proteins / immunology
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Mice
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Models, Molecular
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Protein Binding
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Protein Conformation, alpha-Helical
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Protein Conformation, beta-Strand
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Protein Interaction Domains and Motifs
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Receptors, Scavenger / chemistry*
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Receptors, Scavenger / genetics
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Receptors, Scavenger / immunology
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Receptors, Virus / chemistry*
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Receptors, Virus / genetics
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Receptors, Virus / immunology
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Recombinant Fusion Proteins / chemistry*
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / immunology
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Sequence Alignment
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Sequence Homology, Amino Acid
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Sf9 Cells
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Spodoptera
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Thermodynamics
Substances
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Antibodies, Monoclonal
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Immunoglobulin Fab Fragments
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Lysosomal Membrane Proteins
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Receptors, Scavenger
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Receptors, Virus
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Recombinant Fusion Proteins
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SCARB2 protein, human