title: Predicted conformations for the immunodominant region of the circumsporozoite protein of the human malaria parasite Plasmodium falciparum.
abstract: The circumsporozoite protein of the human malaria parasite Plasmodium falciparum contains multiple tandem repeats of the amino acid sequence Asn-Ala-Asn-Pro. The repeated sequence encompasses the immunodominant region of the protein, and antibodies raised against it are potent inhibitors of invasion and development of sporozoites in cultured hepatocytes. Using a modified build-up procedure, we have explored a large number of possible helical and near-helical conformations of a terminally blocked tetraicosapeptide, consisting of six repeats of the sequence Asn-Ala-Asn-Pro, and conclude that two helical conformations are energetically favored to the exclusion of all others. One of these conformations is longer, thinner, and left-handed and is likely to be adopted in nonpolar environments, while the other is shorter, broader, and right-handed and should be favored in aqueous solutions. We propose that the immunodominant region of the circumsporozoite protein of P. falciparum adopts one of these conformations in vivo.
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000953:Antigens, Protozoan / Q000032:analysis*; D000954:Antigens, Surface / Q000032:analysis*; D000939:Epitopes; D008958:Models, Molecular; D010455:Peptides; D010963:Plasmodium falciparum / Q000276:immunology*; D011487:Protein Conformation; D012997:Solvents; D013816:Thermodynamics
chemical_list: D000953:Antigens, Protozoan; D000954:Antigens, Surface; D000939:Epitopes; D010455:Peptides; D012997:Solvents