Uncovering Common Principles in Protein Export of Malaria Parasites

For proliferation, the malaria parasite Plasmodium falciparum needs to modify the infected host cell extensively. To achieve this, the parasite exports proteins containing a Plasmodium export element (PEXEL) into the host cell. Phosphatidylinositol-3-phosphate binding and cleavage of the PEXEL are t...

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Bibliographic Details
Published in:Cell host & microbe 2012-11, Vol.12 (5), p.717-729
Main Authors: Grüring, Christof, Heiber, Arlett, Kruse, Florian, Flemming, Sven, Franci, Gianluigi, Colombo, Sara F., Fasana, Elisa, Schoeler, Hanno, Borgese, Nica, Stunnenberg, Hendrik G., Przyborski, Jude M., Gilberger, Tim-Wolf, Spielmann, Tobias
Format: Article
Language:English
Subjects:
Animals
Aspartic Acid Endopeptidases - metabolism
Carrier Proteins - metabolism
Humans
Malaria, Falciparum - metabolism
Phosphatidylinositol Phosphates - metabolism
Plasmodium falciparum - metabolism
Protein Transport
Protein Unfolding
Protozoan Proteins - chemistry
Protozoan Proteins - metabolism
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Summary:For proliferation, the malaria parasite Plasmodium falciparum needs to modify the infected host cell extensively. To achieve this, the parasite exports proteins containing a Plasmodium export element (PEXEL) into the host cell. Phosphatidylinositol-3-phosphate binding and cleavage of the PEXEL are thought to mediate protein export. We show that these requirements can be bypassed, exposing a second level of export control in the N terminus generated after PEXEL cleavage that is sufficient to distinguish exported from nonexported proteins. Furthermore, this region also corresponds to the export domain of a second group of exported proteins lacking PEXELs (PNEPs), indicating shared export properties among different exported parasite proteins. Concordantly, export of both PNEPs and PEXEL proteins depends on unfolding, revealing translocation as a common step in export. However, translocation of transmembrane proteins occurs at the parasite plasma membrane, one step before translocation of soluble proteins, indicating unexpectedly complex translocation events at the parasite periphery. ► N termini of processed P. falciparum PEXEL proteins contain a domain required for export ► PEXEL-negative exported proteins (PNEPs) contain a similar export domain ► As with PEXEL proteins, PNEP export depends on protein translocation ► Translocation of PNEPs occurs at the parasite plasma membrane
ISSN:1931-3128
1934-6069
DOI:10.1016/j.chom.2012.09.010