A Plasmodium falciparum PHIST protein binds the virulence factor PfEMP1 and comigrates to knobs on the host cell surface
JournalArticle (Originalarbeit in einer wissenschaftlichen Zeitschrift)
 
ID 2732998
Author(s) Oberli, Alexander; Slater, Leanne M.; Cutts, Erin; Brand, Francoise; Mundwiler-Pachlatko, Esther; Rusch, Sebastian; Masik, Martin F. G.; Erat, Michele C.; Beck, Hans-Peter; Vakonakis, Ioannis
Author(s) at UniBasel Beck, Hans-Peter
Year 2014
Title A Plasmodium falciparum PHIST protein binds the virulence factor PfEMP1 and comigrates to knobs on the host cell surface
Journal The FASEB Journal : official publication of the Federation of American Societies for Experimental Biology
Volume 28
Number 10
Pages / Article-Number 4420-4433
Keywords cytoadherence, exported proteins, interactions, malaria, protein structure
Abstract

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 subtelomeric (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 Kd = 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.

Publisher FASEB
ISSN/ISBN 0892-6638
edoc-URL http://edoc.unibas.ch/dok/A6308523
Full Text on edoc No
Digital Object Identifier DOI 10.1096/fj.14-256057
PubMed ID http://www.ncbi.nlm.nih.gov/pubmed/24983468
ISI-Number WOS:000342222700020
Document type (ISI) Article
 
   

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