Crystal Structure of the Malaria Vaccine Candidate Apical Membrane Antigen 1

• Published in: Science (American Association for the Advancement of Science) Vol. 308; no. 5720; pp. 408 - 411
• Main Authors: Pizarro, Juan Carlos, Normand, Brigitte Vulliez-Le, Chesne-Seck, Marie-Laure, Collins, Christine R, Withers-Martinez, Chrislaine, Hackett, Fiona, Blackman, Michael J, Faber, Bart W, Remarque, Edmond J, Kocken, Clemens H. M, Thomas, Alan W, Bentley, Graham A
• Format: Journal Article
• Language: English
• Published: Washington, DC American Association for the Advancement of Science 15.04.2005; The American Association for the Advancement of Science
• Subjects: Amino Acid Motifs; Amino Acid Sequence; Animals; Antibodies, Monoclonal - immunology; Antigenic determinants; Antigens; Antigens, Protozoan - chemistry; Antigens, Protozoan - immunology; Binding Sites; Biological and medical sciences; Care and treatment; Causes of; Crystal structure; Crystallization; Crystallography, X-Ray; Crystals; Culicidae; Dams; Epitope Mapping; Epitopes; Fundamental and applied biological sciences. Psychology; Genetics; Gross domestic product; Heparin; Heparin - metabolism; Human protozoal diseases; Infectious diseases; Ligands; Literary Devices; Malaria; Malaria Vaccines; Medical research; Medical sciences; Membrane Proteins - chemistry; Membrane Proteins - immunology; Models, Molecular; Molecular Sequence Data; Parasites; Parasitic diseases; Plasmodium falciparum; Plasmodium falciparum - chemistry; Plasmodium falciparum - immunology; Plasmodium vivax; Plasmodium vivax - chemistry; Plasmodium vivax - immunology; Protein Conformation; Protein Folding; Protein Structure, Secondary; Protein Structure, Tertiary; Proteins; Protozoa; Protozoal diseases; Protozoan Proteins - chemistry; Protozoan Proteins - immunology; Receptors; Recombinant Proteins - chemistry; Sequence Alignment; Structure; Testing; Vaccines; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies; France; Infection; Antigen; Protozoa; Plasmodium; Apicomplexa; Protozoal disease; Antigenic determinant; Malaria; Vaccine; Parasitosis; Molecular domain; Structural analysis
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1107449

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.