1H-NMR structures of the Plasmodium falciparum 1758 erythrocyte binding peptide analogues and protection against malaria.
A conserved high activity erythrocyte binding peptide (HAEBP) derived from the 175-erythrocyte binding antigen (EBA-175), coded 1758, was synthesized and analyzed for antigenic and protective activities in Aotus monkeys, together with several of its analogues. Conformational analysis by 1H Nuclear Magnetic Resonance in TFE-solution was done for some of them, as well as the 1758 parent peptide. We show that the conserved 1758 HAEBP (being neither immunogenic nor protective) has an alpha helical structure, whilst its analogues contain beta-turn structures. The 13790 peptide (highly immunogenic and protective for some monkeys) shows a type I beta-turn structure distorted in psi(i + 1) psi(i + 2) angles, whilst immunogenic and non-protective (as well as the non-immunogenic and non-protective peptides) have type III' beta-turns. An understanding of native peptide's correlation with altered peptide three-dimensional structure and resulting immunogenicity and protective activity may lead to a more rational design of multi-antigenic, multi-stage P. falciparum subunit based malaria vaccines.
Guzman
Fanny
F
Fundación Instituto de Inmunología de Colombia (FIDIC), Carrera 50 No. 26-00, Bogotá, Colombia.
Jaramillo
Katherine
K
Salazar
Luz M
LM
Torres
Angela
A
Rivera
Augusto
A
Patarroyo
Manuel E
ME
D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D004912:Erythrocytes / Q000378:metabolism* / Q000469:parasitology; D019084:Fluorescent Antibody Technique, Indirect; D000882:Haplorhini; D016778:Malaria, Falciparum / Q000517:prevention & control*; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism*; D010963:Plasmodium falciparum / Q000378:metabolism* / Q000502:physiology; D011487:Protein Conformation; D011522:Protons; D015800:Protozoan Proteins / Q000737:chemistry / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid
D010446:Peptide Fragments; D011522:Protons; D015800:Protozoan Proteins