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

Protein Cell. 2017 Aug;8(8):590-600. doi: 10.1007/s13238-017-0405-7. Epub 2017 Apr 26.

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

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

Substances

  • Antibodies, Monoclonal
  • Immunoglobulin Fab Fragments
  • Lysosomal Membrane Proteins
  • Receptors, Scavenger
  • Receptors, Virus
  • Recombinant Fusion Proteins
  • SCARB2 protein, human