1. Crystal structure of the malaria vaccine candidate apical membrane antigen 1
- Author
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Pizarro, Juan Carlos, Vulliez-Le Normand, Brigitte, 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., and Bentley, Graham A. more...
- Subjects
Testing ,Care and treatment ,Research ,Causes of ,Vaccines -- Testing -- Research ,Genetics -- Research ,Crystal structure -- Research ,Malaria -- Causes of -- Care and treatment -- Research ,Antigenic determinants -- Research ,Crystals -- Structure - Abstract
Apical membrane antigen 1 (AMA1) is currently in clinical trials as a vaccine against P. falciparum, the species causing the most serious forms of malaria in humans. AMAI is present [...], 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. more...
- Published
- 2005