Mapping a common interaction site used by Plasmodium falciparum Duffy binding-like domains to bind diverse host receptors

Mol Microbiol. 2008 Jan;67(1):78-87. doi: 10.1111/j.1365-2958.2007.06019.x. Epub 2007 Nov 28.

Abstract

The Duffy binding-like (DBL) domain is a key adhesive module in Plasmodium falciparum, present in both erythrocyte invasion ligands (EBLs) and the large and diverse P. falciparum erythrocyte membrane protein 1 (PfEMP1) family of cytoadherence receptors. DBL domains bind a variety of different host receptors, including intercellular adhesion molecule 1 (ICAM-1), a receptor interaction that may have a role in infected erythrocyte binding to cerebral blood vessels and cerebral malaria. In this study, we expressed the nearly full complement of DBLbeta-C2 domains from the IT4/25/5 (IT4) parasite isolate and showed that ICAM-1-binding domains (DBLbeta-C2(ICAM-1)) were confined to group B and group C PfEMP1 proteins and were not present in group A, suggesting that ICAM-1 selection pressure differs between PfEMP1 groups. To further dissect the molecular determinants of binding, we modelled a DBLbeta-C2(ICAM-1) domain on a solved DBL structure and created alanine substitution mutants in two DBLbeta-C2(ICAM-1) domains. This analysis indicates that the DBLbeta-C2::ICAM-1 interaction maps to the equivalent glycan binding region of EBLs, and suggests a general model for how DBL domains evolve under dual selection for host receptor binding and immune evasion.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antigens, Protozoan / chemistry
  • Antigens, Protozoan / genetics
  • Antigens, Protozoan / metabolism*
  • Binding Sites
  • COS Cells
  • Chlorocebus aethiops
  • Host-Parasite Interactions*
  • Intercellular Adhesion Molecule-1 / chemistry
  • Intercellular Adhesion Molecule-1 / genetics
  • Intercellular Adhesion Molecule-1 / metabolism*
  • Models, Molecular
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Phylogeny
  • Plasmodium falciparum / chemistry
  • Plasmodium falciparum / metabolism*
  • Protein Binding
  • Protein Interaction Mapping
  • Protein Structure, Tertiary
  • Protozoan Proteins / chemistry
  • Protozoan Proteins / classification
  • Protozoan Proteins / genetics
  • Protozoan Proteins / metabolism*
  • Receptors, Cell Surface / chemistry
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism*
  • Sequence Alignment
  • Sequence Analysis

Substances

  • Antigens, Protozoan
  • Duffy antigen binding protein, Plasmodium
  • Protozoan Proteins
  • Receptors, Cell Surface
  • erythrocyte membrane protein 1, Plasmodium falciparum
  • Intercellular Adhesion Molecule-1