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Science 10 December 2004:
Vol. 306. no. 5703, pp. 1930 - 1933
DOI: 10.1126/science.1102452
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Reports

Targeting Malaria Virulence and Remodeling Proteins to the Host Erythrocyte

Matthias Marti,* Robert T. Good,* Melanie Rug, Ellen Knuepfer, Alan F. Cowman{dagger}

To establish infection in the host, malaria parasites export remodeling and virulence proteins into the erythrocyte. These proteins can traverse a series of membranes, including the parasite membrane, the parasitophorous vacuole membrane, and the erythrocyte membrane. We show that a conserved pentameric sequence plays a central role in protein export into the host cell and predict the exported proteome in Plasmodium falciparum. We identified 400 putative erythrocyte-targeted proteins corresponding to ~8% of all predicted genes, with 225 virulence proteins and a further 160 proteins likely to be involved in remodeling of the host erythrocyte. The conservation of this signal across Plasmodium species has implications for the development of new antimalarials.

Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria 3050, Australia.



* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: cowman{at}wehi.edu.au

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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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