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

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 (P. fRH), including RH5, have been implicated in invasion...

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Autores:
Tipo de recurso:
Fecha de publicación:
2012
Institución:
Universidad del Rosario
Repositorio:
Repositorio EdocUR - U. Rosario
Idioma:
eng
OAI Identifier:
oai:repository.urosario.edu.co:10336/23459
Acceso en línea:
https://doi.org/10.1016/j.vaccine.2011.11.012
https://repository.urosario.edu.co/handle/10336/23459
Palabra clave:
Binding protein
Chloroquine
Malaria vaccine
Membrane protein
Plasmodium falciparum rh5 protein
Trypsin
Unclassified drug
Amino acid analysis
Amino acid sequence
Article
Binding affinity
Binding competition
Blood sampling
Competitive inhibition
Controlled study
Erythrocyte
Female
Hela cell
Human
Human cell
Immunogenicity
Parasitemia
Peptide mapping
Plasmodium falciparum
Polyacrylamide gel electrophoresis
Priority journal
Protein modification
Protein structure
Protein synthesis
Reversed phase high performance liquid chromatography
Sequence analysis
Structure activity relation
Structure analysis
Western blotting
Amino acid sequence
Amino acid substitution
Animals
Aotus trivirgatus
Carrier proteins
Cell adhesion
Erythrocytes
Humans
Molecular sequence data
Mutant proteins
Plasmodium falciparum
Protein binding
Protein conformation
Sequence alignment
Malaria
Peptide
Receptor
Red blood cell
Structure-activity relationship
Vaccine
missense
Mutation
Rights
License
Abierto (Texto Completo)
Description
Summary: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 (P. fRH), including RH5, have been implicated in invasion as adhesins binding to specific receptors on erythrocyte surface. The regions mediating P. fRH5-RBC specific interactions have been identified here by fine mapping the whole P. fRH5 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 P. fRH5, highlight the inherent difficulties associated with developing a fully effective vaccine against malaria. © 2011 Elsevier Ltd.