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Science 10 December 2004:
Vol. 306. no. 5703, pp. 1934 - 1937
DOI: 10.1126/science.1102737

Reports

A Host-Targeting Signal in Virulence Proteins Reveals a Secretome in Malarial Infection

N. Luisa Hiller, Souvik Bhattacharjee, Christiaan van Ooij, Konstantinos Liolios, Travis Harrison, Carlos Lopez-Estraño,* Kasturi Haldar{dagger}

Malaria parasites secrete proteins across the vacuolar membrane into the erythrocyte, inducing modifications linked to disease and parasite survival. We identified an 11–amino acid signal required for the secretion of proteins from the Plasmodium falciparum vacuole to the human erythrocyte. Bioinformatics predicted a secretome of >320 proteins and conservation of the signal across parasite species. Functional studies indicated the predictive value of the signal and its role in targeting virulence proteins to the erythrocyte and implicated its recognition by a receptor/transporter. Erythrocyte modification by the parasite may involve plasmodial heat shock proteins and be vastly more complex than hitherto realized.

Departments of Pathology and Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, 303 East Chicago Avenue, Chicago, IL 60611, USA.



* Present address: Department of Microbiology and Molecular Cell Sciences, University of Memphis, 3774 Walker Avenue, 409B Life Sciences Building, Memphis, TN 38152, USA.

{dagger} To whom correspondence should be addressed. E-mail: k-haldar{at}northwestern.edu

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