Cell biological characterization of the malaria vaccine candidate trophozoite exported protein 1.
In a genome-wide screen for alpha-helical coiled coil motifs aiming at structurally defined vaccine candidates we identified PFF0165c. This protein is exported in the trophozoite stage and was named accordingly Trophozoite exported protein 1 (Tex1). In an extensive preclinical evaluation of its coiled coil peptides Tex1 was identified as promising novel malaria vaccine candidate providing the rational for a comprehensive cell biological characterization of Tex1. Antibodies generated against an intrinsically unstructured N-terminal region of Tex1 and against a coiled coil domain were used to investigate cytological localization, solubility and expression profile. Co-localization experiments revealed that Tex1 is exported across the parasitophorous vacuole membrane and located to Maurer's clefts. Change in location is accompanied by a change in solubility: from a soluble state within the parasite to a membrane-associated state after export to Maurer's clefts. No classical export motifs such as PEXEL, signal sequence/anchor or transmembrane domain was identified for Tex1.
Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland.
Caroline
C
Kulangara
Samuel
S
Luedin
Olivier
O
Dietz
Sebastian
S
Rusch
Geraldine
G
Frank
Dania
D
Mueller
Mirjam
M
Moser
Andrey V
AV
Kajava
Giampietro
G
Corradin
Hans-Peter
HP
Beck
Ingrid
I
Felger
D000595:Amino Acid Sequence; D000818:Animals; D000953:Antigens, Protozoan / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D001483:Base Sequence; D015153:Blotting, Western; D020126:Brefeldin A / Q000494:pharmacology; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism / Q000469:parasitology*; D015870:Gene Expression; D008288:Malaria / Q000378:metabolism / Q000469:parasitology*; D017780:Malaria Vaccines / Q000276:immunology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018613:Microscopy, Confocal; D008969:Molecular Sequence Data; D015388:Organelles / Q000378:metabolism; D010963:Plasmodium falciparum / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D021381:Protein Transport / Q000187:drug effects; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D011817:Rabbits; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014617:Vacuoles / Q000378:metabolism
D000953:Antigens, Protozoan; D002352:Carrier Proteins; C478484:MAHRP-1 protein, Plasmodium falciparum; D017780:Malaria Vaccines; D008565:Membrane Proteins; C417763:Pfsbp1 protein, Plasmodium falciparum; D015800:Protozoan Proteins; C579321:Tex1 protein, Plasmodium falciparum; D020126:Brefeldin A