Limits...
A Plasmodium falciparum PHIST protein binds the virulence factor PfEMP1 and comigrates to knobs on the host cell surface.

Oberli A, Slater LM, Cutts E, Brand F, Mundwiler-Pachlatko E, Rusch S, Masik MF, Erat MC, Beck HP, Vakonakis I - FASEB J. (2014)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Swiss Tropical and Public Health Institute, Basel, Switzerland; University of Basel, Basel, Switzerland; and.

Show MeSH

Related in: MedlinePlus

Schematic representation of an iRBC knob. Our proposed mechanism of PFE1605w function, connecting the C terminus of PfEMP1 ATS to the cytoskeleton, is illustrated.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4202109&req=5

Figure 8: Schematic representation of an iRBC knob. Our proposed mechanism of PFE1605w function, connecting the C terminus of PfEMP1 ATS to the cytoskeleton, is illustrated.

Mentions: Very recently Proellocks et al. (56) showed that disruption of PFE1605w, termed LyMP in their study, reduced iRBC cytoadherence to CD36 by 55%, while retaining knob formation and PfEMP1 surface localization. Further, they identified an interaction between inside-out vesicles prepared from uninfected human erythrocytes and the PFE1605w positively charged C terminus, but not its PHIST domain. Together with the data presented here, we can now suggest at least one mechanistic role for PFE1605w and potentially for other PHIST proteins in cytoadherence (Fig. 8). We propose that PFE1605w tightly binds to the PfEMP1 intracellular segment (Fig. 1) soon after export from the parasite and remains bound during trafficking to Maurer's clefts (Fig. 4) and eventually knobs (Fig. 3). When in knobs, the C-terminal segment of PFE1605w links PfEMP1 with the host cytoskeleton. The PFE1605w-ATS interaction (Fig. 7) probably complements direct ATS-cytoskeletal binding (57) and ensures mechanical robustness against shear forces exerted by blood flow, thereby allowing strong cytoadherence.


A Plasmodium falciparum PHIST protein binds the virulence factor PfEMP1 and comigrates to knobs on the host cell surface.

Oberli A, Slater LM, Cutts E, Brand F, Mundwiler-Pachlatko E, Rusch S, Masik MF, Erat MC, Beck HP, Vakonakis I - FASEB J. (2014)

Schematic representation of an iRBC knob. Our proposed mechanism of PFE1605w function, connecting the C terminus of PfEMP1 ATS to the cytoskeleton, is illustrated.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4202109&req=5

Figure 8: Schematic representation of an iRBC knob. Our proposed mechanism of PFE1605w function, connecting the C terminus of PfEMP1 ATS to the cytoskeleton, is illustrated.
Mentions: Very recently Proellocks et al. (56) showed that disruption of PFE1605w, termed LyMP in their study, reduced iRBC cytoadherence to CD36 by 55%, while retaining knob formation and PfEMP1 surface localization. Further, they identified an interaction between inside-out vesicles prepared from uninfected human erythrocytes and the PFE1605w positively charged C terminus, but not its PHIST domain. Together with the data presented here, we can now suggest at least one mechanistic role for PFE1605w and potentially for other PHIST proteins in cytoadherence (Fig. 8). We propose that PFE1605w tightly binds to the PfEMP1 intracellular segment (Fig. 1) soon after export from the parasite and remains bound during trafficking to Maurer's clefts (Fig. 4) and eventually knobs (Fig. 3). When in knobs, the C-terminal segment of PFE1605w links PfEMP1 with the host cytoskeleton. The PFE1605w-ATS interaction (Fig. 7) probably complements direct ATS-cytoskeletal binding (57) and ensures mechanical robustness against shear forces exerted by blood flow, thereby allowing strong cytoadherence.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Swiss Tropical and Public Health Institute, Basel, Switzerland; University of Basel, Basel, Switzerland; and.

Show MeSH
Related in: MedlinePlus