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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| Formato: | Artículo (Article) |
| Lenguaje: | Inglés (English) |
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2012
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| Acceso en línea: | https://repository.urosario.edu.co/handle/10336/23459 https://doi.org/10.1016/j.vaccine.2011.11.012 |
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ir-10336-234592022-05-02T12:37:20Z A single amino acid change in the Plasmodium falciparum RH5 (PfRH5) human RBC binding sequence modifies its structure and determines species-specific binding activity Arévalo-Pinzón, Gabriela Curtidor, Hernando Muñoz, Marina Patarroyo, Manuel A. Bermudez, Adriana Patarroyo, Manuel E. 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 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. 2012 2020-05-26T00:02:13Z info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion 0264410X 13588745 https://repository.urosario.edu.co/handle/10336/23459 https://doi.org/10.1016/j.vaccine.2011.11.012 eng info:eu-repo/semantics/openAccess application/pdf instname:Universidad del Rosario |
| institution |
EdocUR - Universidad del Rosario |
| collection |
DSpace |
| language |
Inglés (English) |
| topic |
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 |
| spellingShingle |
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 Arévalo-Pinzón, Gabriela Curtidor, Hernando Muñoz, Marina Patarroyo, Manuel A. Bermudez, Adriana Patarroyo, Manuel E. A single amino acid change in the Plasmodium falciparum RH5 (PfRH5) human RBC binding sequence modifies its structure and determines species-specific binding activity |
| description |
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. |
| format |
Artículo (Article) |
| author |
Arévalo-Pinzón, Gabriela Curtidor, Hernando Muñoz, Marina Patarroyo, Manuel A. Bermudez, Adriana Patarroyo, Manuel E. |
| author_facet |
Arévalo-Pinzón, Gabriela Curtidor, Hernando Muñoz, Marina Patarroyo, Manuel A. Bermudez, Adriana Patarroyo, Manuel E. |
| author_sort |
Arévalo-Pinzón, Gabriela |
| title |
A single amino acid change in the Plasmodium falciparum RH5 (PfRH5) human RBC binding sequence modifies its structure and determines species-specific binding activity |
| title_short |
A single amino acid change in the Plasmodium falciparum RH5 (PfRH5) human RBC binding sequence modifies its structure and determines species-specific binding activity |
| title_full |
A single amino acid change in the Plasmodium falciparum RH5 (PfRH5) human RBC binding sequence modifies its structure and determines species-specific binding activity |
| title_fullStr |
A single amino acid change in the Plasmodium falciparum RH5 (PfRH5) human RBC binding sequence modifies its structure and determines species-specific binding activity |
| title_full_unstemmed |
A single amino acid change in the Plasmodium falciparum RH5 (PfRH5) human RBC binding sequence modifies its structure and determines species-specific binding activity |
| title_sort |
single amino acid change in the plasmodium falciparum rh5 (pfrh5) human rbc binding sequence modifies its structure and determines species-specific binding activity |
| publishDate |
2012 |
| url |
https://repository.urosario.edu.co/handle/10336/23459 https://doi.org/10.1016/j.vaccine.2011.11.012 |
| _version_ |
1740172150509142016 |
| score |
12,131701 |