title: Uncovering common principles in protein export of malaria parasites.
abstract: 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.
authors.affiliation: Bernhard Nocht Institute for Tropical Medicine, Parasitology Section, 20359 Hamburg, Germany.
authors.forename: Christof
authors.initials: C
authors.lastname: Grüring
authors.forename: Arlett
authors.initials: A
authors.lastname: Heiber
authors.forename: Florian
authors.initials: F
authors.lastname: Kruse
authors.forename: Sven
authors.initials: S
authors.lastname: Flemming
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Franci
authors.forename: Sara F
authors.initials: SF
authors.lastname: Colombo
authors.forename: Elisa
authors.initials: E
authors.lastname: Fasana
authors.forename: Hanno
authors.initials: H
authors.lastname: Schoeler
authors.forename: Nica
authors.initials: N
authors.lastname: Borgese
authors.forename: Hendrik G
authors.initials: HG
authors.lastname: Stunnenberg
authors.forename: Jude M
authors.initials: JM
authors.lastname: Przyborski
authors.forename: Tim-Wolf
authors.initials: TW
authors.lastname: Gilberger
authors.forename: Tobias
authors.initials: T
authors.lastname: Spielmann
mesh_terms: D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D006801:Humans; D016778:Malaria, Falciparum / Q000378:metabolism*; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism; D010963:Plasmodium falciparum / Q000378:metabolism*; D021381:Protein Transport; D058767:Protein Unfolding; D015800:Protozoan Proteins / Q000737:chemistry / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D018129:Phosphatidylinositol Phosphates; D015800:Protozoan Proteins; C055525:phosphatidylinositol 3-phosphate; D016282:Aspartic Acid Endopeptidases; C089643:plasmepsin