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Published Online February 24, 2005
Science DOI: 10.1126/science.1107449

Reports

Submitted on November 12, 2004
Accepted on February 7, 2005

Crystal Structure of the Malaria Vaccine Candidate Apical Membrane Antigen 1

Juan Carlos Pizarro 1, Brigitte Vulliez-Le Normand 1, Marie-Laure Chesne-Seck 1, Christine R. Collins 2, Chrislaine Withers-Martinez 2, Fiona Hackett 2, Michael J. Blackman 2, Bart W. Faber 3, Edmond J. Remarque 3, Clemens H.M. Kocken 3, Alan W. Thomas 3, Graham A. Bentley 1*

1 Unité d'Immunologie Structurale, CNRS URA 2185, Institut Pasteur, 25 rue du Dr. Roux, 75724 Paris, France.
2 Division of Parasitology, National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK.
3 Department of Parasitology, Biomedical Primate Research Centre, 2280 GH Rijswijk, The Netherlands.

* To whom correspondence should be addressed.
Graham A. Bentley , E-mail: bentley{at}pasteur.fr

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 Å 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.


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