Identifying Plasmodium falciparum EBA-175 homologue sequences that specifically bind to human erythrocytes.
Erythrocyte binding antigen-160 (EBA-160) protein is a Plasmodium falciparum antigen homologue from the erythrocyte binding protein family (EBP). It has been shown that the EBP family plays a role in parasite binding to the erythrocyte surface. The EBA-160 sequence has been chemically synthesised in seventy 20-mer sequential peptides covering the entire 3D7 protein strain, each of which was tested in erythrocyte binding assays to identify possible EBA-160 functional regions. Five EBA-160 high activity binding peptides (HABPs) specifically binding to erythrocytes with high affinity were identified. Dissociation constants lay between 200 and 460 nM and Hill coefficients between 1.5 and 2.3. Erythrocyte membrane protein binding peptide cross-linking assays using SDS-PAGE showed that these peptides bound specifically to 12, 28, and 44 kDa erythrocyte membrane proteins. The nature of these receptor sites was studied in peptide binding assays using enzyme-treated erythrocytes. HABPs were able to block merozoite in vitro invasion of erythrocytes. HABPs' potential as anti-malarial vaccine candidates is also discussed.
Valbuena
John Jairo
JJ
Fundacion Instituto de Inmunologia de Colombia, Universidad Nacional de Colombia, Colombia. jjval@tutopia.com
Bravo
Ricardo Vera
RV
Ocampo
Marisol
M
Lopez
Ramses
R
Rodriguez
Luis E
LE
Curtidor
Hernando
H
Puentes
Alvaro
A
Garcia
Javier E
JE
Tovar
Diana
D
Gomez
Johana
J
Leiton
Jesus
J
Patarroyo
Manuel Elkin
ME
D000595:Amino Acid Sequence; D000818:Animals; D000953:Antigens, Protozoan / Q000235:genetics* / Q000378:metabolism*; D001665:Binding Sites / Q000235:genetics; D001667:Binding, Competitive; D002942:Circular Dichroism; D004912:Erythrocytes / Q000469:parasitology*; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D010963:Plasmodium falciparum / Q000235:genetics* / Q000276:immunology* / Q000472:pathogenicity; D015800:Protozoan Proteins / Q000235:genetics* / Q000378:metabolism*; D014774:Virulence
D000953:Antigens, Protozoan; D010446:Peptide Fragments; D015800:Protozoan Proteins; C065668:erythrocyte-binding antigen 175, Plasmodium