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A Plasmodium falciparum PHIST protein binds the virulence factor PfEMP1 and comigrates to knobs on the host cell surface
Author(s) -
Oberli Alexander,
Slater Leanne M.,
Cutts Erin,
Brand Françoise,
MundwilerPachlatko Esther,
Rusch Sebastian,
Masik Martin F. G.,
Erat Michèle C.,
Beck HansPeter,
Vakonakis Ioannis
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.14-256057
Subject(s) - plasmodium falciparum , biology , parasite hosting , virulence , microbiology and biotechnology , virulence factor , intracellular , cytoskeleton , malaria , cell , genetics , gene , immunology , world wide web , computer science
Uniquely among malaria parasites, Plasmodium falciparum‐infected erythrocytes (iRBCs) develop membrane protrusions, known as knobs, where the parasite adhesion receptor P. falciparum erythrocyte membrane protein 1 (PfEMP1) clusters. Knob formation and the associated iRBC adherence to host endothelium are directly linked to the severity of malaria and are functional manifestations of protein export from the parasite to the iRBC. A family of exported proteins featuring Plasmodium helical interspersed sub‐telomeric (PHIST) domains has attracted attention, with members being implicated in host‐parasite protein interactions and differentially regulated in severe disease and among parasite isolates. Here, we show that PHIST member PFE1605w binds the PfEMP1 intracellular segment directly with K d = 5 ± 0.6 μM, comigrates with PfEMP1 during export, and locates in knobs. PHIST variants that do not locate in knobs (MAL8P1.4) or bind PfEMP1 30 times more weakly (PFI1780w) used as controls did not display the same pattern. We resolved the first crystallographic structure of a PHIST protein and derived a partial model of the PHIST‐PfEMP1 interaction from nuclear magnetic resonance. We propose that PFE1605w reinforces the PfEMP1‐cytoskeletal connection in knobs and discuss the possible role of PHIST proteins as interaction hubs in the parasite exportome.—Oberli, A., Slater, L. M., Cutts, E., Brand, F., Mundwiler‐Pachlatko, E., Rusch, S., Masik, M. F. G., Erat, M. C., Beck, H.‐P., Vakonakis, I. A Plasmodium falciparum PHIST protein binds the virulence factor PfEMP1 and comigrates to knobs on the host cell surface. FASEB J. 28, 4420–4433 (2014). www.fasebj.org