Conformational analysis of the immunodominant epitopes of the circumsporozoite protein of Plasmodium falciparum and knowlesi.
All of the coat proteins of the sporozoite and merozoite stages of Plasmodium, determined to date, contain tandem repeats and most of these contain at least one proline residue. These tandemly repeated segments of the circumsporozite (CS) proteins of P. falciparum and P. knowlesi have been shown to constitute an immunodominant epitope. Antibodies to these peptide segments have been shown to be protective and cause the shedding of the CS protein, known as the CSP reaction. In this study, four synthetic peptides were prepared by solid-phase peptide synthesis. The first peptide corresponds to the tetrapeptide tandem repeat in the CS protein of P. falciparum, repeated eight times, (NANP)8. The second peptide is an analogue of the first in which glycine is substituted for proline, (NANG)8. The third peptide corresponds to the tandem repeat of P. knowlesi, PK(1-24), which is repeated twice (QAQGDGANAGQP)2. The fourth peptide is a tetrapeptide repeat, corresponding to the C-terminal tetrapeptide of PK(1-24) and is repeated eight times, (AGQP)8. It is shown by CD measurements that the presence of proline in these repeats induces an increase in beta-sheet (beta-turn) content in the (NANP)8 peptide relative to the repeat of (NANG)8 and PK(1-24) peptide in aqueous media. The (AGQP)8 peptide has the highest beta-sheet (beta-turn) content of all peptides studied. The Chou-Fasman predictive algorithm indicates a high beta-turn content in the synthetic peptides. It is concluded that this increase in defined structure correlates well with and hence may contribute to the increased antigenicity in these repeats.
Department of Biochemistry, Brandeis University, Waltham, Massachusetts 02254-9110.
G D
GD
Fasman
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Park
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Schlesinger
D000596:Amino Acids / Q000032:analysis; D000818:Animals; D000953:Antigens, Protozoan / Q000032:analysis / Q000276:immunology*; D002942:Circular Dichroism; D000939:Epitopes; D010455:Peptides / Q000032:analysis / Q000276:immunology; D010961:Plasmodium / Q000276:immunology*; D010963:Plasmodium falciparum / Q000276:immunology*; D011487:Protein Conformation; D015800:Protozoan Proteins
D000596:Amino Acids; D000953:Antigens, Protozoan; D000939:Epitopes; D010455:Peptides; D015800:Protozoan Proteins; C041595:circumsporozoite protein, Protozoan