title: Plasmodium vivax MSP-1 peptides have high specific binding activity to human reticulocytes.
abstract: Plasmodium vivax merozoites have high preferential ability to interact with and invade reticulocytes, although these cells correspond to only 2% of the red blood cells (RBC) population. P. vivax merozoite surface protein-1 (Pv-MSP-1) is believed to have an important role in attachment and invasion process. Using 88 non-overlapping 20-mer peptides, covering the entire Pv-MSP-1 Belem strain sequence, RBC and reticulocyte binding assays were performed. Fourteen sequences were identified with high specific binding activity to reticulocytes, but only three had high specific binding activity to mature erythrocytes. These peptides showed affinity constant values between 20 and 150nM, indicating a strong interaction between these sequences and reticulocyte receptors. Critical residues in binding to reticulocytes for these peptides were determined by competition binding assays with glycine scanning analogues. All high binding peptides bind to reticulocyte surface proteins having a molecular mass of around 18-20kDa which are not present in mature RBC. Interestingly, some high activity binding peptides (HABPs) are located close to the hypothesised 42 and 19kDa fragment cleavage sites for this protein, suggesting that these sequences have an important role in target cell attachment and invasion process by Pv-MSP-1.HABPs may be clustered in two regions, with region I being located between amino acids 280-719, and region II between amino acids 1060-1599 with higher than 25% identity level. A P. falciparum MSP-1 antigenic domain binds to RBCs and inhibits parasite invasion. Peptides 1721 and 1724 bind with high activity to reticulocytes in homologous Pv-MSP-1, suggesting similar functions for these two sequences.
authors.affiliation: Fundación Instituto de Inmunología de Colombia, Universidad Nacional de Colombia, Carrera 50, No. 26-00, Bogotá, Colombia. luchorodriguezp@yahoo.es
authors.forename: Luis Eduardo
authors.initials: LE
authors.lastname: Rodríguez
authors.forename: Mauricio
authors.initials: M
authors.lastname: Urquiza
authors.forename: Marisol
authors.initials: M
authors.lastname: Ocampo
authors.forename: Hernando
authors.initials: H
authors.lastname: Curtidor
authors.forename: Jorge
authors.initials: J
authors.lastname: Suárez
authors.forename: Javier
authors.initials: J
authors.lastname: García
authors.forename: Ricardo
authors.initials: R
authors.lastname: Vera
authors.forename: Alvaro
authors.initials: A
authors.lastname: Puentes
authors.forename: Ramses
authors.initials: R
authors.lastname: López
authors.forename: Martha
authors.initials: M
authors.lastname: Pinto
authors.forename: Zuly
authors.initials: Z
authors.lastname: Rivera
authors.forename: Manuel Elkin
authors.initials: ME
authors.lastname: Patarroyo
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002352:Carrier Proteins / Q000378:metabolism; D006801:Humans; D020066:Merozoite Surface Protein 1 / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D010966:Plasmodium vivax / Q000276:immunology*; D012156:Reticulocytes / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D020066:Merozoite Surface Protein 1