title: Crystal structure of the malaria vaccine candidate apical membrane antigen 1.
abstract: Apical membrane antigen 1 from Plasmodium is a leading malaria vaccine candidate. The protein is essential for host-cell invasion, but its molecular function is unknown. The crystal structure of the three domains comprising the ectoplasmic region of the antigen from P. vivax, solved at 1.8 angstrom resolution, shows that domains I and II belong to the PAN motif, which defines a superfamily of protein folds implicated in receptor binding. We also mapped the epitope of an invasion-inhibitory monoclonal antibody specific for the P. falciparum ortholog and modeled this to the structure. The location of the epitope and current knowledge on structure-function correlations for PAN domains together suggest a receptor-binding role during invasion in which domain II plays a critical part. These results are likely to aid vaccine and drug design.
authors.affiliation: Unité d'Immunologie Structurale, Centre National de la Recherche Scientifique, URA 2185, Institut Pasteur, 25 rue du Docteur Roux, 75724 Paris, France.
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Pizarro
authors.forename: Brigitte
authors.initials: B
authors.lastname: Vulliez-Le Normand
authors.forename: Marie-Laure
authors.initials: ML
authors.lastname: Chesne-Seck
authors.forename: Christine R
authors.initials: CR
authors.lastname: Collins
authors.forename: Chrislaine
authors.initials: C
authors.lastname: Withers-Martinez
authors.forename: Fiona
authors.initials: F
authors.lastname: Hackett
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Blackman
authors.forename: Bart W
authors.initials: BW
authors.lastname: Faber
authors.forename: Edmond J
authors.initials: EJ
authors.lastname: Remarque
authors.forename: Clemens H M
authors.initials: CH
authors.lastname: Kocken
authors.forename: Alan W
authors.initials: AW
authors.lastname: Thomas
authors.forename: Graham A
authors.initials: GA
authors.lastname: Bentley
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000953:Antigens, Protozoan / Q000737:chemistry* / Q000276:immunology; D001665:Binding Sites; D003460:Crystallization; D018360:Crystallography, X-Ray; D018604:Epitope Mapping; D000939:Epitopes; D006493:Heparin / Q000378:metabolism; D017780:Malaria Vaccines; D008565:Membrane Proteins / Q000737:chemistry* / Q000276:immunology; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010963:Plasmodium falciparum / Q000737:chemistry / Q000276:immunology; D010966:Plasmodium vivax / Q000737:chemistry / Q000276:immunology*; D011487:Protein Conformation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D015800:Protozoan Proteins / Q000737:chemistry* / Q000276:immunology; D011994:Recombinant Proteins / Q000737:chemistry; D016415:Sequence Alignment
chemical_list: D000911:Antibodies, Monoclonal; D000953:Antigens, Protozoan; D000939:Epitopes; D017780:Malaria Vaccines; D008565:Membrane Proteins; D015800:Protozoan Proteins; D011994:Recombinant Proteins; C090077:apical membrane antigen I, Plasmodium; D006493:Heparin