A novel Plasmodium falciparum erythrocyte binding protein-2 (EBP2/BAEBL) involved in erythrocyte receptor binding

Mol Biochem Parasitol. 2002 Feb;119(2):159-68. doi: 10.1016/s0166-6851(01)00428-5.

Abstract

The 175-kDa erythrocyte binding protein (EBA-175) of Plasmodium falciparum and Duffy antigen binding proteins of P. vivax and P. knowlesi are members of a protein family. The features of this protein family include a cysteine-rich motif present in the erythrocyte receptor-binding domain. We identify here a novel 140-kDa P. falciparum erythrocyte binding protein (EBP2/BAEBL) containing the signature cysteine-rich motif by comparative analysis of gene sequence information. Polyclonal antibodies generated by immunization with an EBP2/BAEBL DNA vaccine immunoprecipitated a 140-kDa protein from P. falciparum schizont-infected erythrocyte lysates. Similar to EBA-175, the binding of EBP2/BAEBL to human erythrocytes was dependent on sialic acids because neuraminidase treatment of those erythrocytes rendered them incapable of binding, but differed from EBA-175 in that trypsin treatment decreased EBP2/BAEBL binding by only twofold compared to a 10-fold reduction in EBA-175 binding. Antibodies raised against the putative erythrocyte-binding domain of EBP2/BAEBL effectively blocked the binding of native EBP2/BAEBL to erythrocytes. These functional antibodies localize EBP2/BAEBL to the invasive apical end of the merozoite. We identify EBP2/BAEBL as a paralogue of EBA-175 and as a novel P. falciparum vaccine candidate.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs
  • Amino Acid Sequence
  • Animals
  • Antigens, Protozoan*
  • Blotting, Western
  • Carrier Proteins / chemistry
  • Carrier Proteins / genetics*
  • Carrier Proteins / immunology
  • Carrier Proteins / metabolism*
  • Cysteine / genetics
  • Cysteine / metabolism
  • Gene Order
  • Humans
  • Immunoglobulin G / immunology
  • Immunoglobulin G / pharmacology
  • Membrane Glycoproteins / metabolism*
  • Membrane Proteins
  • Mice
  • Mice, Inbred BALB C
  • Molecular Sequence Data
  • Plasmodium falciparum / genetics*
  • Protein Binding
  • Protozoan Proteins / chemistry
  • Protozoan Proteins / genetics*
  • Protozoan Proteins / immunology
  • Protozoan Proteins / metabolism*
  • Receptors, Cell Surface / chemistry
  • Receptors, Cell Surface / genetics*
  • Receptors, Cell Surface / immunology
  • Receptors, Cell Surface / metabolism*
  • Receptors, Immunologic / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Homology, Amino Acid
  • Sialic Acid Binding Ig-like Lectin 1

Substances

  • Antigens, Protozoan
  • Carrier Proteins
  • Duffy antigen binding protein, Plasmodium
  • Immunoglobulin G
  • Membrane Glycoproteins
  • Membrane Proteins
  • Protozoan Proteins
  • Receptors, Cell Surface
  • Receptors, Immunologic
  • SIGLEC1 protein, human
  • Sialic Acid Binding Ig-like Lectin 1
  • Siglec1 protein, mouse
  • erythrocyte binding protein-2, Plasmodium falciparum
  • erythrocyte-binding antigen 175, Plasmodium
  • Cysteine

Associated data

  • GENBANK/AF425236
  • GENBANK/AY030048
  • GENBANK/AY030049
  • GENBANK/AY052371