Alpha helix shortening in 1522 MSP-1 conserved peptide analogs is associated with immunogenicity and protection against P. falciparum malaria.
1522 is a nonimmunogenic conserved high-activity binding peptide (HABP) belonging to Plasmodium falciparum MSP-1 protein N-terminal fragment. The key amino acids in binding to red blood cells (RBC) were identified and replaced by others having similar mass but different charge. Because conserved HABPs are not antigenic nor immunogenic, immunogenicity and protectivity studies were then conducted on them in the Aotus monkey. 1H-NMR studies included the lead peptide 1522 as well as the analogs 9782, 13446, 13448, and 13442 to relate their structure to biological function. All the peptides presented alpha-helical structure, with differences observed in helix location and extension. The nonprotective 1522 peptide was totally helical from the N- to the C-terminus, very similar to nonprotective 13442 and 13448 peptides whose extension was almost totally helical. The 9782 and 13446 protective peptides, however, possessed a shorter helical region where modified critical binding residues were not included. A more flexible region was generated at the C-terminus in those peptides with a shorter helical region, leading to a greater number of conformers. These data suggest that peptide flexibility results in increased interaction with immune system molecules, generating protective immunity.
Cubillos
Marcia
M
Fundación Instituto de Inmunología de Colombia, Bogotá, Colombia.
Espejo
Fabiola
F
Purmova
Jindra
J
Martinez
Juan C
JC
Patarroyo
M E
ME
D000595:Amino Acid Sequence; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D001029:Aotus trivirgatus; D001665:Binding Sites; D017124:Conserved Sequence; D017780:Malaria Vaccines; D016778:Malaria, Falciparum / Q000276:immunology / Q000517:prevention & control*; D020066:Merozoite Surface Protein 1 / Q000737:chemistry* / Q000276:immunology*; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D010446:Peptide Fragments / Q000737:chemistry* / Q000276:immunology* / Q000378:metabolism; D010455:Peptides / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D017433:Protein Structure, Secondary
D000913:Antibodies, Protozoan; D017780:Malaria Vaccines; D020066:Merozoite Surface Protein 1; D010446:Peptide Fragments; D010455:Peptides