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Originally published in Science Express on 24 February 2005
Science 15 April 2005:
Vol. 308. no. 5720, pp. 408 - 411
DOI: 10.1126/science.1107449
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Reports

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. Bentley1*

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.

1 Unité d'Immunologie Structurale, Centre National de la Recherche Scientifique, URA 2185, Institut Pasteur, 25 rue du Docteur 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, Netherlands.

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

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