Skip to main content
main-content

01.12.2017 | Research | Ausgabe 1/2017 Open Access

Malaria Journal 1/2017

Tryptophan-rich domains of Plasmodium falciparum SURFIN4.2 and Plasmodium vivax PvSTP2 interact with membrane skeleton of red blood cell

Zeitschrift:
Malaria Journal > Ausgabe 1/2017
Autoren:
Xiaotong Zhu, Yang He, Yifan Liang, Osamu Kaneko, Liwang Cui, Yaming Cao
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1186/​s12936-017-1772-5) contains supplementary material, which is available to authorized users.

Abstract

Background

Plasmodium falciparum dramatically alters the morphology and properties of the infected red blood cells (iRBCs). A large group of exported proteins participate in these parasite-host interactions occurring at the iRBC membrane skeleton. SURFIN4.2 is one of iRBC surface protein that belongs to surface-associated interspersed protein (SURFIN) family. Although the intracellular tryptophan-rich domain (WRD) was proposed to be important for the translocation of SURFINs from Maurer’s clefts to iRBC surface, the molecular basis of this observation has yet to be defined. The WRDs of P. falciparum SURFIN proteins and their orthologous Plasmodium vivax subtelomeric transmembrane proteins (PvSTPs) show homology to the intracellular regions of PfEMP1 and Pf332, both of which are involved in RBC membrane skeleton interactions, and contribute to malaria pathology.

Methods

Two transfected lines expressing recombinant SURFINs (NTC-GFP and NTC-4.2WRD2-GFP) of the 3D7 sequence were generated by transfection in P. falciparum. In vitro binding assays were performed by using recombinant WRDs of SURFIN4.2/PvSTP2 and inside-out vesicles (IOVs). The interactions between the recombinant WRDs of SURFIN4.2/PvSTP2 with actin and spectrin were evaluated by the actin spin down assay and an enzyme-linked immunosorbent assay based binding assays, respectively.

Results

The recombinant SURFINs (NTC-4.2WRD2-GFP), in which the second WRD from SURFIN4.2 was added back to NTC-GFP, show diffused pattern of fluorescence in the iRBC cytosol. Furthermore, WRDs of SURFIN4.2/PvSTP2 were found to directly interact with the IOVs of RBC, with binding affinities ranging from 0.26 to 0.68 μM, values that are comparable to other reported parasite proteins that bind to the RBC membrane skeleton. Further experiments revealed that the second WRD of SURFIN4.2 bound to F-actin (K d = 5.16 μM) and spectrin (K d = 0.51 μM).

Conclusions

Because PfEMP1 and Pf332 also bind to actin and/or spectrin, the authors propose that the interaction between WRD and RBC membrane skeleton might be a common feature of WRD-containing proteins and may be important for the translocation of these proteins from Maurer’s clefts to the iRBC surface. The findings suggest a conserved mechanism of host-parasite interactions and targeting this interaction may disrupt the iRBC surface exposure of Plasmodium virulence-related proteins.
Zusatzmaterial
Literatur
Über diesen Artikel

Weitere Artikel der Ausgabe 1/2017

Malaria Journal 1/2017 Zur Ausgabe

Neu im Fachgebiet Innere Medizin

Mail Icon II Newsletter

Bestellen Sie unseren kostenlosen Newsletter Update Innere Medizin und bleiben Sie gut informiert – ganz bequem per eMail.

© Springer Medizin 

Bildnachweise