title: P. falciparum pro-histoaspartic protease (proHAP) protein peptides bind specifically to erythrocytes and inhibit the invasion process in vitro.
abstract: Plasmodium falciparum histoaspartic protease (HAP) is an active enzyme involved in haemoglobin degradation. HAP is expressed as an inactive 51-kDa zymogen and is cleaved into an active 37-kDa enzyme. It has been proposed that this kind of protease might be implicated in the parasite's invasion of erythrocytes; however, this protein's role during invasion has still to be determined. Synthetic peptides derived from the HAP precursor (proHAP) were tested in erythrocyte binding assays to identify their possible function in the invasion process. Two proHAP high-activity binding peptides (HABPs) specifically bound to erythrocytes; these peptides were numbered 30609 (101LKNYIKESVKLFNKGLTKKS120) and 30610 (121YLGSEFDNVELKDLANVLSF140 ). The binding of these two peptides was saturable, presenting nanomolar affinity constants. These peptides interacted with 26- and 45-kDa proteins on the erythrocyte surface; the nature of these receptor sites was studied in peptide binding assays using enzyme-treated erythrocytes. The HABPs showed greater than 90% merozoite invasion inhibition in in vitro assays. Goat serum containing proHAP polymeric peptide antibodies inhibited parasite invasion in vitro .
authors.affiliation: Fundacion Instituto de Inmunologia de Colombia (FIDIC), Cra 50 26-00, Bogotá, Colombia. jjval@tutopia.com
authors.forename: John
authors.initials: J
authors.lastname: Valbuena
authors.forename: Ricardo
authors.initials: R
authors.lastname: Vera
authors.forename: Alvaro
authors.initials: A
authors.lastname: Puentes
authors.forename: Marisol
authors.initials: M
authors.lastname: Ocampo
authors.forename: Javier
authors.initials: J
authors.lastname: Garcia
authors.forename: Hernando
authors.initials: H
authors.lastname: Curtidor
authors.forename: Ramses
authors.initials: R
authors.lastname: Lopez
authors.forename: Luis
authors.initials: L
authors.lastname: Rodriguez
authors.forename: Jaiver
authors.initials: J
authors.lastname: Rosas
authors.forename: Jimena
authors.initials: J
authors.lastname: Cortes
authors.forename: Martha
authors.initials: M
authors.lastname: Forero
authors.forename: Martha
authors.initials: M
authors.lastname: Pinto
authors.forename: Manuel Elkin
authors.initials: ME
authors.lastname: Patarroyo
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000097:blood*; D004912:Erythrocytes / Q000201:enzymology*; D006801:Humans; D008969:Molecular Sequence Data; D008970:Molecular Weight; D010446:Peptide Fragments / Q000378:metabolism*; D010963:Plasmodium falciparum / Q000201:enzymology* / Q000472:pathogenicity; D011485:Protein Binding / Q000502:physiology
chemical_list: D010446:Peptide Fragments; D016282:Aspartic Acid Endopeptidases