Functional analysis of membrane associated histidine rich proteins of Plasmodium falciparum

• Research unit: COST
• Project number: C05.0043

Key words (English)

Malaria; Proteomics; Protein analysis; Histidine rich proteins; trafficking

Research programs (English)

COST-Action 857 - Apicomplexian Biology in the Post-Genomic Era

Short description (English)

Our proteomic analysis of early transcribed genes of the malaria parasite Plasmodium falciparum revealed the first two membrane bound histidine rich proteins (Spielmann and Beck 2000). Histidine rich proteins are important molecules both as structural proteins and as detoxifying divalent metal binding proteins. Because the identified proteins also localize to the peculiar parastie derived structures in the erythrocyte cytoplasm called Maurer's clefts, they could become also major targets for interventions. But most importantly, both molecules are extremely useful to elucidate the biogenesis of the Maurer's clefts and to study trafficking processes beyond the parasite's confines in this extremely important human parasite. In this project we will further analyse the localization of the molecules, their biochemical properties, and by making various transgenic constructs will elucidate both trafficking processes and the biogenesis of Maurer's clefts.

Partners and International Organizations (English)

AT, CZ, DK, FR, DE, EL, IT, NL, NO, PT, ES, SE, CH, UK

Abstract (English)

Our proteomic analysis of early transcribed genes of the malaria parasite Plasmodium falciparum revealed the first two membrane bound histidine rich proteins (Spielmann and Beck 2000). Histidine rich proteins are important molecules both as structural proteins and as detoxifying divalent metal binding proteins. Because the identified proteins also localize to the peculiar parastie derived structures in the erythrocyte cytoplasm called Maurer's clefts, they could become also major targets for interventions. But most importantly, both molecules are extremely useful to elucidate the biogenesis of the Maurer's clefts and to study trafficking processes beyond the parasite's confines in this extremely important human parasite. In this project we have further analysed the localization of the molecules, their biochemical properties, and made various transgenic constructs to elucidate both trafficking processes and the biogenesis of Maurer's clefts (Spycher et al. 2006). We furthermore were able to generate a MAHRP1 negative mutant which showed no obvious phenotype in culture, but we were able to demonstrate that the major viirulence factor of P. falciparum, the PfEMP1 molecule cannot be found anymore on the surface of the infected erythrocyte. This MAHRP1 negative mutation provides us with a very useful tool to also study the intracellular transport of the major virulence determinant in P. falciparum.

References in databases (English)

Swiss Database: COST-DB of the State Secretariat for Education and Research Hallwylstrasse 4 CH-3003 Berne, Switzerland Tel. [phone] Swiss Project-Number: C05.0043