Identification of Exported Plasmodium falciparum Proteins That Bind to the Erythrocyte Cytoskeleton

Shakya, Bikash; Kilili, Geoffrey Kimiti; Wang, Ling; Nakayasu, Ernesto S.; LaCount, Douglas J.

doi:10.3390/microorganisms10071438

Identification of Exported Plasmodium falciparum Proteins That Bind to the Erythrocyte Cytoskeleton

Journal Article · Sat Jul 16 00:00:00 EDT 2022 · Microorganisms

DOI:https://doi.org/10.3390/microorganisms10071438· OSTI ID:2471606

^[1]; Kilili, Geoffrey Kimiti ^[1]; Wang, Ling ^[1]; ^[2]; ^[1]

Purdue University, West Lafayette, IN (United States)
Purdue University, West Lafayette, IN (United States); Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)

Plasmodium proteins are exported to the erythrocyte cytoplasm to create an environment that supports parasite replication. Although hundreds of proteins are predicted to be exported through Plasmodium export element (PEXEL)-dependent and -independent mechanisms, the functions of exported proteins are largely uncharacterized. In this study, we used a biochemical screening approach to identify putative exported P. falciparum proteins that bound to inside-out vesicles prepared from erythrocytes. Out of 69 P. falciparum PEXEL-motif proteins tested, 18 bound to inside-out vesicles (IOVs) in two or more independent assays. Using co-affinity purifications followed by mass spectrometry, pairwise co-purification experiments, and the split-luciferase assay, we identified 31 putative protein–protein interactions between erythrocyte cytoskeletal proteins and predicted exported P. falciparum proteins. We further showed that PF3D7_1401600 binds to the spectrin-binding domain of erythrocyte ankyrin via its MESA erythrocyte cytoskeleton binding (MEC) motif and to the N-terminal domains of ankyrin and 4.1R through a fragment that required an intact Plasmodium helical interspersed sub-telomeric (PHIST) domain. Introduction of PF3D7_1401600 into erythrocyte ghosts increased retention in the microsphiltration assay, consistent with previous data that reported a reduction of rigidity in red blood cells infected with PF3D7_1401600-deficient parasites.

View Accepted Manuscript (DOE)

Research Organization:: Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)

Sponsoring Organization:: National Institutes of Health (NIH); USDOE Office of Science (SC), Basic Energy Sciences (BES). Scientific User Facilities (SUF)

Grant/Contract Number:: AC05-76RL01830

OSTI ID:: 2471606

Journal Information:: Microorganisms, Journal Name: Microorganisms Journal Issue: 7 Vol. 10; ISSN 2076-2607

Publisher:: MDPICopyright Statement

Country of Publication:: United States

Language:: English

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59 BASIC BIOLOGICAL SCIENCES
PF3D7_1401600
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ankyrin
band 4.1
cytoskeleton
erythrocyte
exported protein
host–pathogen interaction
microbiology
red blood cell

Identification of Exported Plasmodium falciparum Proteins That Bind to the Erythrocyte Cytoskeleton

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