A single amino acid change in the Plasmodium falciparum RH5 (PfRH5) human RBC binding sequence modifies its structure and determines species-specific binding activity

Vaccine. 2012 Jan 11;30(3):637-46. doi: 10.1016/j.vaccine.2011.11.012. Epub 2011 Nov 17.


Identifying the ligands or regions derived from them which parasites use to invade their target cells has proved to be an excellent strategy for identifying targets for vaccine development. Members of the reticulocyte-binding homologue family (PfRH), including RH5, have been implicated in invasion as adhesins binding to specific receptors on erythrocyte surface. The regions mediating PfRH5-RBC specific interactions have been identified here by fine mapping the whole PfRH5 protein sequence. These regions, called high activity binding peptides (HABPs), bind to a receptor which is sensitive to trypsin treatment and inhibit merozoite invasion of RBCs by up to 80%, as has been found for HABP 36727. Our results show that a single amino acid change in the HABP 36727 sequence modifies a peptide's 3D structure, thereby resulting in a loss of specific binding to human RBCs and its inhibition ability, while binding to Aotus RBC remains unmodified. Such invasion differences and binding ability produced by replacing a single amino acid in an essential molecule, such as PfRH5, highlight the inherent difficulties associated with developing a fully effective vaccine against malaria.

MeSH terms

  • Amino Acid Sequence
  • Amino Acid Substitution*
  • Animals
  • Aotus trivirgatus
  • Carrier Proteins / chemistry
  • Carrier Proteins / genetics*
  • Carrier Proteins / metabolism*
  • Cell Adhesion*
  • Erythrocytes / metabolism
  • Erythrocytes / parasitology*
  • Humans
  • Molecular Sequence Data
  • Mutant Proteins / chemistry
  • Mutant Proteins / genetics
  • Mutant Proteins / metabolism
  • Mutation, Missense*
  • Plasmodium falciparum / pathogenicity*
  • Protein Binding
  • Protein Conformation
  • Sequence Alignment


  • Carrier Proteins
  • Mutant Proteins
  • RH5 protein, Plasmodium falciparum