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Epitope mirroring between the malaria surface proteins PfGARP and PIESP2 identifies a knob-associated complex in infected erythrocytes
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DOI：10.1016/j.jbc.2026.113291.png)
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Abstract
En 中文
Malaria is a life-threatening infectious disease responsible for an estimated 610,000 deaths each year, with the greatest burden falling on children in sub-Saharan Africa. A defining feature of infection by the most lethal human malaria parasite, Plasmodium falciparum, is the adhesion of infected red blood cells (iRBCs) to vascular endothelial cells. This cytoadhesion is mediated by distinctive knob-like protrusions unique to P. falciparum and plays a central role in the pathogenesis of cerebral and placental malaria contributing to seizures, coma, and adverse pregnancy outcomes. Despite decades of intensive efforts to target highly polymorphic PfEMP1 anchored on knobs, no effective therapeutic interventions targeting this pathway have yet been developed. Using phage display cDNA technology, we previously identified a malaria antigen called Plasmodium falciparum glutamic acid-rich protein (PfGARP), which binds to host erythrocyte membrane anion exchanger-1 protein (Band 3). To further investigate the composition of the PfGARP complex, we generated and characterized a monoclonal antibody, termed GM7mAb, that recognizes an epitope located within the repetitive regions of PfGARP. By combining unbiased mass spectrometry and two independent PfGARP-null parasite lines, here we report identification of a reverse epitope recognized by GM7mAb within Parasite-Infected Erythrocyte Specific Protein-2 (PIESP2). These findings demonstrate the presence of a subpopulation of PIESP2 localized to the surface of knobs, and utility of GM7mAb as a diagnostic tool for the detection of antibodies against PIESP2 in a malaria-endemic region. Further characterization of the knob-associated PIESP2 complex may yield novel insights into strategies for disrupting cytoadherence in cerebral and pregnancy-associated malaria.
Keywords:
Plasmodium falciparum
PfGARP
PIESP2
Band 3
Knob
Cytoadhesion
RBC
red blood cell
PfEMP1
Plasmodium falciparum erythrocyte membrane protein 1
PfGARP
P. falciparum glutamic acid-rich protein
PIESP2
Parasite-Infected Erythrocyte Specific Protein-2
DIDS
4,4'-diisothiocyanato-2,2'-stilbenedisulphonate
KAHRP
Knob-Associated Histidine-Rich Protein
CSA
chondroitin sulfate A
PBST
0.05% Tween-20
HMS
Harvard Medical School
NIH
National Institutes of Health
Journal
IF:
3.9
Papers:
11.2W
Citations:
28.3W
Organization
Cited Papers