NMR structure of Plasmodium falciparum malaria peptide correlates with protective immunity.
Apical membrane antigen-1 is an integral Plasmodium falciparum malaria parasite membrane protein. High activity binding peptides (HABPs) to human red blood cells (RBCs) have been identified in this protein. One of them (peptide 4313), for which critical binding residues have already been defined, is conserved and nonimmunogenic. Its critical binding residues were changed for amino acids having similar mass but different charge to change such immunological properties; these changes generated peptide analogues. Some of these peptide analogues became immunogenic and protective in Aotus monkeys.Three-dimensional models of peptide 4313 and three analogues having different immune characteristics, were calculated from nuclear magnetic resonance (NMR) experiments with distance geometry and restrained molecular dynamic methods. All peptides contained a beta-turn structure spanning amino acids 7 to 10, except randomly structured 4313. When analysing dihedral angle phi and psi values, distorted type III or III' turns were identified in the protective and/or immunogenic peptides, whilst classical type III turns were found for the nonimmunogenic nonprotective peptides. This data shows that some structural modifications may lead to induction of immunogenicity and/or protection, suggesting a new way to develop multicomponent, subunit-based malarial vaccines.
Purmova
Jindra
J
Fundación Instituto de Inmunología de Colombia (FIDIC), Bogotá, Colombia.
Salazar
Luz Mary
LM
Espejo
Fabiola
F
Torres
Mary Helena
MH
Cubillos
Marcia
M
Torres
Elizabeth
E
Lopez
Yolanda
Y
Rodríguez
Raul
R
Patarroyo
Manuel Elkin
ME
D000595:Amino Acid Sequence; D000818:Animals; D000913:Antibodies, Protozoan / Q000096:biosynthesis; D001029:Aotus trivirgatus; D001665:Binding Sites; D015153:Blotting, Western; D017124:Conserved Sequence; D009682:Magnetic Resonance Spectroscopy; D017780:Malaria Vaccines; D013058:Mass Spectrometry; D020066:Merozoite Surface Protein 1 / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010963:Plasmodium falciparum / Q000276:immunology*; D015800:Protozoan Proteins / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage*
D000913:Antibodies, Protozoan; D017780:Malaria Vaccines; D020066:Merozoite Surface Protein 1; D015800:Protozoan Proteins; D014614:Vaccines, Synthetic